Health Canada responds to Expert Advisory Panel on COX-2 drugs

Health Canada today responded to the release of the report of the Expert Advisory Panel on selective COX-2 non-steroidal anti-inflammatory drugs (NSAIDs). The panel issued its recommendations earlier today.


"We welcome the panel's report and I'd like to thank the public for its contribution," Health Minister Ujjal Dosanjh said. "This is the first time that the Canadian public has been invited to participate in a Health Canada expert advisory panel. Health Canada supports the direction of the Panel's recommendations. Openness and transparency will become a way of doing business in the Department.


"I am not only impressed by the quality of the report, but also by the fact that the panel has made important suggestions that will further advance our plans for making important health and safety information more accessible," the Minister said.


Health Canada will immediately implement many of the panel's recommendations and we will work with our partners to see what further action can be taken.


Health Canada acknowledges the panel's view that, as a group, selective COX-2 inhibitors are associated with an increased risk of cardiovascular events, a risk that is similar to those associated with most NSAIDs. The panel noted that this risk is present for all patients taking anti-inflammatory agents and that it increases with longer-term use and when other risk factors, such as cardiovascular disease, are present.


Health Canada also acknowledges the panel's findings that certain drugs in this class are effective anti-inflammatory agents and that the use of these drugs should be left to informed patients, advised by their well-informed health care providers.


In the case of Vioxx, which is not currently authorized for sale in Canada, the panel reported that available data justifies the marketing of Vioxx in Canada because the risk of cardiovascular incidents from Vioxx appears to be similar to that of most NSAIDs. In order for VIOXX to be marketed in Canada, the manufacturer is required to submit a new drug submission to Health Canada. The submission would be carefully reviewed to ensure it meets safety data requirements, with particular attention to the safe labelling issues raised by the panel.


Immediate actions Health Canada will take include:


* Manufacturers of all NSAIDs currently on the market in Canada will be requested to provide updated patient safety information for these products. This would include Celebrex, which is currently available in Canada by prescription, and ibuprofen products currently available over-the-counter;


* Health Canada will continue its assessment of whether Bextra should be returned to the Canadian market after sales were voluntarily suspended in April 2005. The recommendations from the panel will be a key factor in the Department's final decision, which is expected in the coming weeks;















* Health Canada will be conducting further analysis and communicating to provincial health regulators the panel's recommendations on current over-the-counter availability of some ibuprofen products, in particular to address the possibility of inappropriate, long-term use of these products;


* Health Canada will issue guidance to manufacturers, establishing standards for the risk and benefit information that must be included in product labelling of NSAIDs.


"Health Canada's initiatives will not stop there," Minister Dosanjh said. "The public can rest assured that Health Canada will continue to act in the best interests of protecting the health of Canadians. Health Canada will also follow up on other recommendations made by the panel."


Over the longer term:


* Health Canada will continue to work with the Canadian Medical Association, the Canadian Pharmaceutical Association, The Arthritis Society, and other professional associations and consumer organizations to ensure that consistent safety information about NSAIDs is provided to health care professionals and the public;


* Health Canada endorses the panel's recommendation that all information associated with drug submissions and clinical trials be publicly available. The Minister has clearly stated his preference for full disclosure, with the exception of legitimate and compelling reasons of privacy or business confidentiality. This is the direction in which Health Canada will be moving;


* Health Canada will work with the Pharmaceutical Advertising Advisory Board to ensure safety information is appropriately reflected in advertising for this class of drugs;


* Health Canada will continue to strengthen cooperation with national associations of health care professionals to encourage and support the development of clinical practice guidelines describing the benefits and risks of COX-2 inhibitors and NSAIDs.


In line with the panel's recommendations on increased transparency of drug information, Health Canada has already undertaken the following initiatives:


* A recently completed public consultation on clinical trial registration and disclosure. Feedback gleaned from these consultations will be made public and will be used to help Health Canada develop options for facilitation the registration and disclosure of clinical trial information in Canada


* A new Web-based database on adverse drug reactions in Canada


* A discussion paper entitled, Designing a Mandatory System for Reporting Serious Adverse Reaction is posted on Health Canada's web site. The Department invites all interested stakeholders and the public to review the document and provide feedback. Face-to-face consultations with stakeholders and the public will be held late summer.


In the coming weeks, additional databases will be launched to increase Canadians' access to information on drug safety.


The panel, which met June 9-10, 2005 in Ottawa, was created by Health Canada to provide input and advice on the safety of COX-2 NSAIDs and was one part of an extensive review and study of research related to the safety of these drugs.

Custom-Made Insoles Offer Relief To Sufferers Of Foot Pain

Custom-made insoles known as foot orthoses can reduce foot pain caused by arthritis, overly prominent big toe joints and highly arched feet, a new systematic review shows.



A team of Cochrane Researchers found that custom orthoses were safe interventions for foot pain in a number of different conditions. However, more research is required to develop an in depth understanding of their effectiveness.



Approximately one in four people are affected by foot pain at any given time. It is often disabling and can impair mood, behaviour, self-care ability and overall quality of life. People suffer from foot pain for a variety of reasons, but pain is more common in the elderly and those with chronic conditions such as arthritis. In the majority of cases, patients undergo a combination of different treatments, one of which may be custom-made foot orthoses (insoles moulded to a cast of the foot).



The Cochrane Systematic Review focuses on the results of 11 trials that together involved 1,332 people. Researchers found that custom foot orthoses can relieve pain within three months in adults with rheumatoid arthritis, as well as in children with juvenile idiopathic arthritis, an early onset form of the disease. Adults with painful highly arched feet or painfully prominent big toe joints also benefited from treatment with orthoses over three and six month periods respectively.



"Custom foot orthoses can be an effective treatment for a variety of conditions, but there are still many causes of foot pain for which the benefit of this treatment is unclear. There is also a lack of data on the long term effects of treating with orthoses," says Fiona Hawke, the lead researcher, who works at the Central Coast campus of the University of Newcastle, Australia.







News from The Cochrane Library



Source: Jennifer Beal


Wiley-Blackwell

Stanford research shows targeted DNA vaccine may reverse autoimmune disease

Contact: Mitzi Baker

650-725-2106

Stanford University Medical Center


STANFORD, Calif. - Stanford University Medical Center researchers have developed a way to tailor therapies to combat the specific inappropriate responses of autoimmune diseases in mice.


The researchers also have shown that their technique can provide information needed to predict a disease's progression.


Eventually, their work may provide a way to reverse the course of such autoimmune diseases in humans as multiple sclerosis, rheumatoid arthritis and type-1 diabetes by first identifying the immune system culprits gone awry and then creating customized therapies for individual patients.


Researchers Bill Robinson, P. J. Utz and Lawrence Steinman published results last year showing how microarrays - glass slides spotted with minute amounts of the proteins against which the body may be reacting - can provide a profile of the antibodies' targets.

Their current work, which appears in the September issue of Nature Biotechnology, takes the technology a step further and shows that the pattern of antibody activation can be used to predict and treat animals suffering from a disease resembling M.S.



'Ultimately, we think the array can be used to guide patient-specific therapy,' said Robinson, MD, PhD, assistant professor of medicine (immunology and rheumatology) and lead author of the study.

For example, a blood sample from a patient thought to have M.S. could be profiled using the array to help identify whether the person is likely to progress to full-blown disease and whether the individual would benefit from therapy. The information obtained in the profile could then be used to personalize therapies.



The team, which included former Stanford researcher Hideki Garren, MD, PhD, showed that this strategy works in a mouse model of M.S. called experimental autoimmune encephalomyletis, or EAE.


In both conditions, the immune system launches an attack against the myelin sheath, the fatty cells that insulate neurons from electricity and ensure the speedy transmission of nerve impulses.

Neurons that have patches of myelin destroyed by M.S. or EAE short-circuit and can lead to a variety of neurological disorders, depending on the part of the brain affected.



'Looking at one M.S. marker at a time had previously not been terribly informative,' said Robinson. 'We thought that looking at thousands at once would be more fruitful.'

Thanks to a dozen or so labs around the world that shared their protein samples, the group rapidly produced a comprehensive array that covered hundreds of the myelin sheath proteins.



When they analyzed serum samples from EAE mice using the array, they found that each mouse had a unique pattern of reactivity. Based on their antibody profiles, mice whose immune systems were attacking more elements on the myelin sheath progressed to a more severe disease, while mice whose immune systems made more restricted responses did not progress and had fewer flare-ups.














The group then designed a treatment to reverse the progression of the disease, treating mice that had already suffered an initial attack of paralysis.



Autoimmune responses are thought to develop when antibodies attack many different proteins in the organ being targeted, so Robinson and his colleagues wanted to find a therapy that specifically knocked out as many of the harmful responses as possible while leaving the rest of the immune system functional.


To do so, they took advantage of a well-known but poorly understood process known as tolerization. In this process, the immune system is coaxed to tolerate an offending protein after injection of that same protein or pieces of it. Utz, MD, assistant professor of medicine (immunology and rheumatology), likens the process to allergy shots: the agent causing the allergic reaction is injected into muscle in order for the body to learn to ignore it.



Using the microarray information to guide them to the targets of the autoimmune response in the sickest mice, Garren and Steinman, MD, professor of neurology and neurological sciences, built on previous studies in Steinman's lab to create a tolerizing vaccine that delivered four of the targeted proteins.

To make an effective delivery vehicle, they put the DNA sequence that encoded the proteins into a circular piece of DNA called a plasmid, creating a DNA vaccine. When these engineered plasmids were injected, they produced the desired proteins and a programmed tolerization process began.



One advantage of DNA vaccines over other methods of tolerization, Garren noted, is that it allows for multiple autoimmune targets to be tolerized simultaneously rather than one at a time. 'We found that this approach broadly turns off autoimmune responses,' said Robinson.

'Clinically, the animals do better when receiving the vaccine. When we use our arrays to monitor the response, we see broad reductions in the progression of the disease.'



The ability to profile which antibodies have gone awry has a number of implications for diagnosis and treatment of people with autoimmune diseases.

'When we see these patients, we have no idea what is going to happen 10 years from now,' Utz said. 'It would be great to have a test that would let us know if a person is going to have a horrible outcome so we could treat aggressively, or if a person is going to be fine, or if a person is going to have a bad response to a therapy so we could avoid that.'



Led by Steinman, the team plans to use their findings to help people with autoimmune diseases. To reach this goal, they co-founded Bayhill Therapeutics; Garren directs the scientific efforts of the company.



Using DNA vaccines to specifically turn off the immune system is a completely new way to immunize, said Steinman. 'This is the opposite of what we try to do with traditional vaccines against bacteria and viruses, where we want to stimulate the immune system to attack the microbe,' he added.



This study was funded by a number of sources, including funds from a $14.7 million contract from the National Institutes of Health, the Baxter Foundation and the Arthritis Foundation.



Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at mednews.stanford.



PRINT MEDIA CONTACT: Mitzi Baker at (650) 725-2106 (mitzibakerstanford)

BROADCAST MEDIA CONTACT: M.A. Malone at (650) 723-6912 (mamalonestanford)

Merck To Pay $32 Million Damages In Texas Vioxx Case

A court in Rio Grande City, Texas, has awarded the family of Leonel Garza $7 million in compensatory damage and $25 million in punitive damages. Merck was sued by Leonel Garza's family, which alleged that Vioxx led to his fatal heart attack in 2001. Garza was 71 when he died.


Merck is facing over 11,000 lawsuits. There have been six so far, Merck has lost half of them. Even if one tenth of the eleven thousand suits remaining went the wrong way for Merck, the total payout would be huge. Imagine an average payout of $20 million, multiply that by 1,000 successful cases for the plaintiffs, and you have a tidy figure of $20,000,0000,000.


Vioxx was taken off the market because of significant cardiovascular risks for patients who took it for longer than 18 months.


As in the recent New Jersey case, Merck says it will appeal.


Each time a verdict awarding damages is published, Merck's share value drops a bit. When this news came out, Merck shares fell 26 cents to close at $34.74 in the New York Stock Exchange.


Perhaps Merck's strategy of taking each lawsuit individually may have been a mistake


Written by:




View drug information on Vioxx.

TAU Researcher Maps Drug Target To Wipe Pain Away

In most cases of chronic pain - lingering pain that never seems to go away after accidents or prolonged illnesses - no pill exists to dull the hurt. Billions of dollars are lost every year in sick days taken to alleviate chronic pain, and as much money is spent by the healthcare system to diagnose what's wrong.



Dr. Joel Hirsch of Tel Aviv University conducts basic research investigating calcium channels in the human body, established targets for the alleviation of chronic pain. His research, recently presented at the Biophysical Society in San Francisco, provides new information into how these channels work. His laboratory is developing computer-derived models of drugs that might affect chronic pain - such as pain from backaches, sore limbs and arthritis - which are targeted for calcium channels.



"We have determined structures of calcium channel components which provide a framework for drug design and targeting," Dr. Hirsch says. "There is still much to learn about calcium channels, which enable pain signals to travel from the body to the brain."



Once he and his colleagues understand the deeper mechanisms of these channels, they hope to use new drugs to modulate them "on" and "off" as needed - and provide relief to the millions of people who suffer from the condition.



Finding where it hurts



According to the American Chronic Pain Association, chronic pain is pain that persists a month or more beyond the usual recovery period for an injury or illness. It can continue for months or years, is not always constant, but usually interferes with one's quality of life at all levels.



Three drugs on the market target calcium channels for pain indications such as Lyrica®, Neurotonin and ziconitide. But they are not effective in many cases, while ziconitide requires an injection into the spine. Hence, there is a considerable need for alternative drugs.



"Calcium channels are still poorly understood, but we do know that they are also important players in pathways that cause epilepsy. Our research into neuropathy, or finding treatments for chronic pain, may yield a new class of compounds that serve multiple purposes," says Dr. Hirsch. "Our challenge is to target calcium channel modulators to specific tissues or channel types a single drug for all forms of chronic pain isn't likely.



"There are literally millions of people that already take calcium channel blockers for angina and hypertension. More research on how this family of channels works could yield a new kind of drug for a specific subfamily of these channels," Dr. Hirsch concludes.



Source:

George Hunka

American Friends of Tel Aviv University


View drug information on Lyrica.

Many Rheumatoid Arthritis Sufferers Forced Into Early Retirement

A joint study on "The Burden of Rheumatoid Arthritis and Patient Access to Treatments" by authors from the Stockholm School of Economics (Sweden), the University of Lund (Sweden) and the Medical University of Vienna (Austria) has shown that the highest cost in rheumatoid arthritis results from patients having to leave the workforce early due to the disease. The study has just been published online in a supplement to Springer's The European Journal of Health Economics.??



Rheumatoid arthritis (RA) is one of the most common autoimmune diseases and a leading cause of chronic pain affecting over three million people in Europe alone.



Lead author Professor Bengt J?¶nsson from the Stockholm School of Economics explained: "The study highlights the significant variation in patient access to disease-modifying biologic drugs for the treatment of RA. This is important because medical data have shown that early treatment with these drugs reduces inflammation and can prevent or reduce the speed of joint damage and hence the progression of affected individuals to disability."



The total annual economic impact of rheumatoid arthritis is estimated at ?‚¬42 billion in Western Europe and ?‚¬3.4 billion in Eastern Europe (2006 figures). Improved treatment strategies as well as the application of 'biologic' rheumatoid arthritis drugs have been shown in randomized clinical trials to increase the chances for remission, halting of the progression of joint damage and improvement or prevention of disability. The study also concluded that patient access to the new drugs in Europe is very low in a number of member states and varies significantly between the EU and the US. The uptake of the drugs in the US was shown to be about three times higher than that of Western Europe.



"The costs of the drugs must be viewed within the overall cost of the disease and the benefit of these drugs over the long term, that is in relation to their positive health impact and the savings that should eventually result from this", health economist Dr. Gisela Kobelt said.



Up to two-thirds (65 percent) of costs for rheumatoid arthritis patients are outside the health care sector - such as productivity losses, patient out-of-pocket costs and informal care. Early retirement due to the disease is frequent, with up to 50 percent of those living with rheumatoid arthritis forced to leave the workforce and apply for a disability pension within ten years of disease onset.



"Of all the chronic diseases, rheumatoid arthritis has one of the biggest impacts on the quality of life of patients," said Professor Josef Smolen, a rheumatologist at the Medical University of Vienna. "I am confident that this study will contribute to the discussion on the importance of RA from a societal perspective and not just a health care perspective. Patient access to good care and treatment including thorough follow-up examinations and access to innovative drug therapies, where indicated, are critical elements that will benefit all of society..."







The European Journal of Health Economics (eurekalert/pub_releases/2008-02/springer/journal/10198) is a highly scientific and at the same time practical oriented journal considering the requirements of various health care systems in Europe. Springer (springer/) is the second-largest publisher of journals in the science, technology, and medicine (STM) sector and the largest publisher of STM books. Springer is part of Springer Science+Business Media, one of the world's leading suppliers of scientific and specialist literature.



Funding for the study was provided through an unrestricted educational grant by F. Hoffmann La Roche Ltd.



Reference

??J?¶nsson B, Kobelt G, Smolen J (Guest Editors). 2008. The Burden of Rheumatoid Arthritis and Patient Access to Treatment. The European Journal of Health Economics. Vol. 8, Suppl. 2 / January 2008



Source: Joan Robinson


Springer

Contribution Of Obesity To Decreased Mobility In High Functioning Older Women With Osteoarthritis

Osteoarthritis, common among older adults, is strongly linked to late-life disability, but the process by which this happens has not been well studied. A recent study published in the April 2006 issue of Arthritis Care & Research (interscience.wiley/journal/arthritiscare) examined the impact of osteoarthritis in the lower extremities and found that women with this condition have a greater risk of developing decreased mobility, a risk which is further increased by being overweight.


Led by Shari M. Ling of Intramural Research Program, National Institute on Aging/NIH together with investigators in the Center on Aging and Health at the Johns Hopkins Medical Institutions in Baltimore, MD, researchers used data obtained from participants in the Women's Health and Aging Study II (WHAS II) to determine whether patients with osteoarthritis in their lower extremities were more prone to developing mobility limitations than women who did not have the disease.

They also looked at whether limitations in mobility tended to develop before difficulty in activities of daily living. Their analysis included 199 women with lower extremity osteoarthritis who had no difficulty with mobility tasks at the beginning of the study and 140 women without osteoarthritis in the knee or hip, all of whom were between 70 and 79 years old. Patients were evaluated as to their osteoarthritis status, the presence of pain, knee strength, knee torque, and their level of mobility 18, 36 and 72 months following the initial evaluation.


The results showed that even though more women with osteoarthritis reported using arthritis medications, a greater proportion reported having pain most days and greater pain severity while walking and climbing stairs compared to women with no OA. In addition, 26% of the women with osteoarthritis were obese compared to 11% of the women without the disease, and an additional 40% were overweight. The two groups were similar, however, with regard to knee strength and torque.

Overall, women with osteoarthritis were about 2.5 times more likely to develop difficulty in both lower extremity mobility and activities of daily living than those who did not have osteoarthritis. Greater knee strength reduced the risk of developing difficulty performing daily activities whether or not the woman had osteoarthritis, and greater knee torque had the same effect, although it did not reduce the risk for lower extremity difficulty.


"Despite numerous cross-sectional reports of the associations between OA [osteoarthritis], painful symptoms, low strength and obesity, existing studies have not been able to discern the relative contributions of these closely related factors to the development of specific mobility difficulty characteristics," the authors note.

The current study demonstrates that lower extremity osteoarthritis is associated with painful symptoms, excess weight and obesity and that women with painful osteoarthritis are more likely to develop lower extremity limitations combined with limitations on their daily activities. The fact that this is affected by higher body mass is what lends novelty to the current study, according to the authors.


"Longitudinal observations of well-functioning women living in the community who are at risk of functional decline provide a unique perspective from which OA can be examined," the authors state. The findings of the current study are particularly relevant given the increase in the number of older Americans and the trend to higher rates of obesity among Americans in all age groups. The authors conclude: "The trends towards earlier onset of obesity observed between 1991 and 1998 would predictably translate into a higher proportion of adults who could develop painful symptoms and mobility difficulty at an earlier age."


Article : "Transitions to Mobility Difficulty Associated With Lower Extremity Osteoarthritis in High Functioning Older Women: Longitudinal Data from the Women's Health and Aging Study II," Shari M. Ling, Qian Li Xue, Eleanor M. Simonsick, Jing Tian, Karen Bandeen-Roche, Linda P. Fried, Joan M. Bathon, Arthritis Care & Research, April 2006; 55:2; pp.


For more information visitinterscience.wiley/journal/arthritis





© 2005 American College of Rheumatology
rheumatology

Early Treatment With Infliximab And Methotrex For Rheumatoid Arthritis Has Led To 1/5 Of Patients In Drug-Free Remission

Early treatment with a combination of methotrexate and infliximab may be effective as remission induction therapy and alter the course of early rheumatoid arthritis (RA), according to data presented at EULAR 2007, the Annual European Congress of Rheumatology in Barcelona, Spain.



At four year follow up, over half (51%) of the patients who started treatment with a combination of methotrexate and infliximab in the BeSt ('Behandel-Strategie?«n' or 'treatment strategies') trial had been able to discontinue treatment with infliximab and maintained a good response (Disease Activity Score (DAS) ?‰¤2.4). 41 patients were still taking methotrexate monotherapy at trial end. Almost one in five (17%) of patients had reached clinical remission (DAS

Invatec Launches First Drug-Eluting Balloon Designed To Treat Atherosclerosis Below The Knee

Invatec, a comprehensive innovator of interventional products, announced the European launch of a new peripheral balloon, the IN.PACT™ Amphirion paclitaxel-eluting PTA balloon catheter. This is the first drug-eluting catheter designed specifically to treat atherosclerosis in arteries located below the knee (BtK). IN.PACT features FreePac™, a proprietary coating that frees and separates paclitaxel molecules and facilitates their absorption into the wall of the artery.


The FreePac coating was developed in close collaboration with the researchers who pioneered drug-eluting balloon therapy, Ulrich Speck, Ph.D., Department of Mitte, Berlin and Bruno Scheller, M.D., University Radiology at Charite Hospital, Department of Internal Medicine, Homburg/Saar. "According to research published in the New England Journal of Medicine1 and Circulation2, drug-eluting balloons utilizing a special drug elution formulation have demonstrated effectiveness in the treatment of atherosclerosis and the prevention of restenosis," commented Andrea Venturelli and Stefan Widensohler, co-founders of Invatec. "Invatec is taking this approach further by offering a drug elution therapy targeted specifically for below the knee interventions and placing it on a market-leading, state-of-the-art platform, the Amphirion Deep balloon catheter."


Invatec plans to launch a randomized trial, the IN.PACT DEEP study, in the first half of 2009, to provide additional data about the effectiveness of this new treatment concept.


"After years of research we are pleased to see this technology available for clinical applications," commented Prof. Speck and Prof. Scheller. "The drug-eluting balloon concept has the potential to reduce re-intervention rates for patients with atherosclerosis. Invatec's balloon technology is an ideal platform for the FreePac coating and will allow for the development of specific solutions for additional endovascular applications including the superficial femoral artery (SFA)."


Prof. Dierk Scheinert, course director of the LINC interventional course in Leipzig, commented on the first IN.PACT Amphirion procedure, "Combining conventional balloon dilatation with local drug administration is a fascinating new concept for this patient group. Stents may not be a feasible option for the majority of BtK patients with advanced disease. The IN.PACT Amphirion therefore holds promise as an effective treatment for this challenging patient population."


Impaired blood flow caused by blockages below the knee, also known as Critical Limb Ischemia (CLI) result in pain, poor wound healing, gangrene and a high risk of death. According to data published in Wounds, 40 percent of patients require amputation within 12 months of a CLI episode, and there is an annual mortality rate of more than 20 percent.


In addition to IN.PACT Amphirion, Invatec offers a full, dedicated product line for below the knee artery treatment, including the Amphirion™ DEEP 0.014" balloon catheter, the 0.014" Skipper™ DEEP guide wire, the Chromis™ DEEP 0.014" balloon-expandable stent and the new Maris™ DEEP 0.018" self-expandable stent.


About Invatec


Invatec is a comprehensive innovator of vascular interventional products with global headquarters based in Italy. Driven by research and technology, Invatec actively collaborates with physicians and centers of excellence to develop products that will improve life expectancy and quality of life for patients. The company's core competencies include polymer processing, metal technology and surface technology. Invatec is vertically integrated with full in-house capabilities to design, develop, manufacture and assemble the 35 product families that are offered in more than 70 countries. Dedicated to "making ideas come alive," the company was founded in 1996 by Andrea Venturelli and Stefan Widensohler, and has grown to almost 1000 employees. For more information, visit invatec.


1 THUNDER trial (N Engl J Med 2008;358:689-99), ISR-Paccocath (N Engl J Med 2006;355:2113-24)


2 FemPac Trial (Circulation. 2008;118:1358-1365)

Invatec

Life USA, Inc.'s Enhanced Metabolics Introduces New Product For Joint Health

Life USA, Inc. (OTC
Bulletin Board: LFUI), a distributor of natural products based in Boulder,
Colorado. Today announced the introduction of AgilFlex(TM) Joint Health
Formula under the company's Enhanced Metabolics brand. This combination of
two proprietary, clinically backed ingredients features the antioxidant
power of NKO(TM) (Neptune Krill Oil) from Neptune Technologies &
Bioressources Inc. of Laval, Quebec, Canada, a current Enhanced Metabolics
product offering, and the joint mobility complex SierraSil (registered
trademark) of Sierra Mountain Minerals of Vancouver, Canada.


AgilFlex, a unique blend of ingredients from a high altitude mountain
range and a remote ocean, is a fast-acting, safe, 100% natural formula that
promotes joint mobility and an active lifestyle. NKO(TM), a primary
ingredient in AgilFlex, is a sustainable harvested, Antarctic Ocean-derived
organism that is mercury-free, rich in Omega 3's, and high in antioxidants
and phospholipids. SierraSil, the other primary ingredient, is derived from
a distinct, naturally-occurring mineral composite (found only in the high
Sierra Mountains of Canada) that promotes joint mobility, flexibility, a
healthy response to inflammation, and protects cartilage from breakdown.


"We are very excited to be able to offer these two special ingredients
as one unique formula," said Michael Schuett, Life USA President, "The
ingredients in AgilFlex have demonstrated tremendous results with regard to
promoting joint health, an issue everyone has to face regardless of their
level of activity." He added, "This formula is all about improving quality
of life."


Safe Harbor Statement under the Private Securities Litigation Reform
Act of 1995: This release contains forward-looking information. Statements
that are not descriptions of historical facts are forward-looking
statements provided under the "safe harbor" protection of the Private
Securities Litigation Reform Act of 1995. These statements are made to
enable a better understanding of our business, but because these
forward-looking statements are subject to many risks, uncertainties, future
developments and changes over time, actual results may differ materially
from those expressed or implied by such forward-looking statements.
Examples of forward-looking statements are statements about anticipated
financial or operating results, financial projections, business prospects,
future product performance and other matters that are not historical facts.
Such statements often include words such as "believes," "expects,"
"anticipates," "intends," "plans," "estimates" or similar expressions.


These forward-looking statements are based on the information that was
currently available to us, and the expectations and assumptions that were
deemed reasonable by us, at the time the statements were made. We do not
undertake any obligation to update any forward-looking statements in this
report or in any of our other communications, except as required by law,
and all such forward-looking statements should be read as of the time the
statements were made, and with the recognition that these forward-looking
statements may not be complete or accurate at a later date.


Life USA, Inc.

EnhancedMetabolics

Myth That Exercise and Arthritis Don't Mix Still Lingers

Most patients still believe
something other than exercise is the most effective non-drug
treatment for osteoarthritis, according to a new poll by
Spine-health.


The Spine-health poll of 897 back pain patients shows
that 53% of patients chose options besides exercise as the
best course of action for treating osteoarthritis pain and
inflammation. Eighteen percent chose "heat/ice", 12% chose
"rest", 12% chose "manipulation (e.g.,
chiropractic/osteopathic adjustments)", 9% chose
"acupuncture" and 2% chose "support devices (e.g., a
brace)".


"For years, people with arthritis thought the right answer
was to avoid activity, physical therapy and exercise, for
fear that their pain would get worse. Well, avoiding
activity and exercise is actually the wrong answer," says
Vert Mooney, M.D., an orthopedic spine surgeon in San Diego,
and author of a new article published on Spine-health
about spinal osteoarthritis treatment options. "The common
thread among most osteoarthritis patients successfully
managing their condition, including reducing pain and
improving movement, is regular exercise. While the poll
results show that more and more people understand the role
of exercise in helping improve osteoarthritis symptoms,
there is work to do in adequately busting the myth that
arthritis and exercise don't mix."


Of the several varieties of arthritis, the most common,
disabling and often the most painful is osteo- (meaning
bone) arthritis, mostly affecting knees, hips, hands, feet
and the spine. Osteoarthritis, also known as degenerative
joint disease, affects up to 30 million Americans, mostly
women and usually those over 45 or 50 years of age.
Normally, joints have remarkably little friction and move
easily, but with degeneration of the joint, the cartilage
becomes rough and likely worn out - causing the joint halves
to rub against each other, creating pain and limiting
motion.


For those with osteoarthritis, exercise should focus on
strengthening the muscles around the joints (removing some
stress from the joints), improving joint mobility and
reducing joint stiffness and pain. The recommended
categories of exercise usually include strengthening (done
on resistance or weight machines or with exercise bands),
low impact aerobics, and range of motion exercises. Popular
activities for arthritis sufferers include gentle exercises
such as swimming and other water therapy, walking,
stationary cycling, yoga, even golf. "The key is making the
patient's muscles work harder (not necessarily faster or
longer) than they usually do with normal daily activity.
However, exercise needs to be done correctly to avoid
causing further joint pain and should be guided by an
appropriately trained physical therapist or other
professional," adds Dr. Mooney.


Further information on osteoarthritis and treatment options,
including exercise, medication, and surgery, can be viewed
at spine-health.


About Spine-health


Spine-healthprovides in-depth information and resources
for patients with back pain, neck pain, and a full range of
spinal disorders. Written and peer-reviewed by spine
specialists, the site includes thousands of pages of
original articles, animations, clinical trials, and spine
physician web pages.

Mutation In Bone Marrow Cancers Blocked By Promising New Drug , May Also Help Patients With Rheumatoid Arthritis

Oregon Health & Science University Knight Cancer Institute researchers have found that an experimental drug successfully blocks an enzyme that causes some bone marrow cancers.



The oral drug, called CYT387, was tested in mice as well as in human cells. In both cases, it blocked the growth of certain bone marrow cancers called myeloproliferative disorders, also referred to as MPDs.



The research was presented Tuesday, Dec. 9, at 7 a.m. during the 50th annual American Society of Hematology conference in San Francisco.



"The drug was found to be very effective against a specific type of cancer cells, cancer cells which are driven by an enzyme mutation called JAK2-V617F. In the mouse model, the drug blocked JAK2-V617F, normalized blood counts and reduced enlarged spleens back to a normal size. It is a very promising compound," said Thomas Bumm, M.D., Ph.D., a member of the research team.



The drug works by binding to the V617F mutation in the JAK2 enzyme. Without this drug, the mutated JAK2 enzyme leads to MPDs. The "big three" MPDs include polycythemia vera, essential thrombocythemia and primary myelofibrosis. Until now there have been no FDA-approved targeted treatments for these diseases.



"Based on the efficacy that we demonstrated in the mouse model, there is a good chance that CYT387 will enter clinical trials as early as 2009. Those in greatest need include patients with myelofibrosis, a relentless disease for which there is currently no effective therapy. It is likely that JAK2 inhibitors will change the standard of care for these patients," said Michael Deininger, M.D., Ph.D., principal investigator and Head of the Hematological Malignancies Program Ph.D. He also is an associate professor of medicine (hematology/medical oncology), OHSU School of Medicine and a Scholar of the Leukemia & Lymphoma Society.



Researchers also discovered that CYT387 effectively blocks overproduction of inflammatory cytokines. Abnormal cells carrying the JAK2-V617F mutation produce a large amount of different inflammatory cytokines that help the cancer cells to grow and repress normal cells. In mice, the drug normalized 19 different inflammatory cytokine levels in the blood. The overproduction of cytokines can also be found in inflammatory conditions such as rheumatoid arthritis. This drug's effect on cytokines could benefit patients with inflammatory diseases, especially rheumatoid arthritis.



The next likely step will be to open clinical trials for people with MPD as soon as 2009 once formal preclinical toxicology studies are completed.







The investigational drug is made by Cytopia Research Pty Ltd, a publicly registered drug company from Australia. Cytopia sponsored this trial.



Other researchers include: Jeffrey Tyner, Ph.D.; Jutta Deininger, M.D., senior research assistant; Jonathan Van Dyke, research assistant; Marc Loriaux, M.D., Ph.D., assistant professor of pathology (anatomic pathology) and assistant professor of medicine (hematology/medical oncology); and Brian Druker, M.D., director of the OHSU Knight Cancer Institute, JELD-WEN Chair of Leukemia Research, Howard Hughes Medical Institute Investigator and a member of the National Academy of Sciences.



About the OHSU Knight Cancer Institute



The OHSU Cancer Institute is the only National Cancer Institute-designated center between Sacramento and Seattle. It comprises some 200 clinical researchers, basic scientists and population scientists who work together to translate scientific discoveries into longer and better lives for Oregon's cancer patients. In the lab, basic scientists examine cancer cells and normal cells to uncover molecular abnormalities that cause the disease. This basic science informs more than 300 clinical trials conducted at the OHSU Cancer Institute.



About OHSU



Oregon Health & Science University is the state's only health and research university and Oregon's only academic health center. OHSU is Portland's largest employer and the fourth largest in Oregon (excluding government), with 12,400 employees. OHSU's size contributes to its ability to provide many services and community support activities not found anywhere else in the state. It serves patients from every corner of the state, and is a conduit for learning for more than 3,400 students and trainees. OHSU is the source of more than 200 community outreach programs that bring health and education services to every county in the state.



Source: Christine Decker


Oregon Health & Science University

Synthetic human protein eases acute and chronic arthritis symptoms in mice

A lab-made version of a human protein alleviates symptoms of both acute and chronic arthritis in mice and could be the basis for a new arthritis drug for people, report scientists from the National Institute of Allergy and Infectious Disease (NIAID), part of the National Institutes of Health (NIH). The protein prevents the assembly of a cell surface receptor, thus blocking transmission of chemical signals that lead to arthritis symptoms.


"This study opens a new research avenue to better understand and, perhaps, to treat rheumatoid arthritis, a condition that causes suffering in more than two million Americans," says NIAID Director Anthony S. Fauci, M.D.


Investigators from NIAID's Laboratory of Immunology, led by Michael Lenardo, M.D., published their findings in the October issue of Nature Medicine, now available online. The idea that the protein, called pre-ligand assembly domain protein or PLAD, might play a role in thwarting the joint inflammation characteristic of rheumatoid arthritis--one of the most common autoimmune diseases--grew out of their research on a very rare autoimmune disease called autoimmune lymphoproliferative syndrome (ALPS).


Previously, Dr. Lenardo and his colleagues showed that in ALPS a form of PLAD blocks a cell surface receptor and prevents a needed chemical signaling pathway from functioning correctly. In ALPS, the signal pathway interrupted by PLAD leads to disease symptoms. But, the scientists reasoned, PLAD might also be able to block a related cell surface receptor--one involved in passing signals that lead to inflammation. In theory, inhibiting this pathway might benefit people with rheumatoid arthritis, who suffer from excessive inflammation.


A key promoter of inflammation is a chemical called tumor necrosis factor alpha (TNF-alpha). TNF-alpha starts a chemical chain reaction leading to inflammation by binding to two cell surface receptors, TNFR-1 and TNFR-2. Naturally occurring PLAD helps both forms of TNFR assemble and prepare to receive TNF-alpha. Synthetic PLAD, the scientists hypothesized, would bind to its natural counterpart and prevent it from performing its usual task.


The scientists used a variety of techniques (including injection of TNF-alpha) to induce arthritis symptoms in mice. Researchers also injected some of the animals with lab-made PLAD (P60 PLAD). "We found that P60 PLAD protein powerfully inhibited the symptoms of TNF-alpha-induced arthritis," says Dr. Lenardo. P60 PLAD also lessened the effects of arthritis induced by other means. Moreover, he adds, P60 PLAD appeared to inhibit disease symptoms in mice with established as well as acute arthritis. The scientists did not detect any obvious toxicity in the PLAD-treated mice.


"We're very hopeful that this could be good news for arthritis sufferers," says Dr. Lenardo. In particular, the researchers are intrigued by P60 PLAD's apparent specificity: it seems to block the binding of TNF-alpha to TNFR-1, while allowing TNFR-2 to continue to function. This is important, notes Dr. Lenardo, because it may represent an advantage over some currently used arthritis drugs, which directly block TNF-alpha by binding to both TNFRs and thereby inhibit beneficial actions mediated by TNFR-2.















The scientists next aim to develop a more stable form of P60 PLAD. Ultimately, they hope to test the protein in clinical trials.


The research was also supported by the National Institute of General Medical Sciences, part of the NIH.


NIAID is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.


Reference: G-M Deng et al. Amelioration of inflammatory arthritis by targeting the pre-ligand assembly domain (PLAD) of tumor necrosis factor receptors. Nature Medicine. Published online September 18, 2005. DOI: 10.1038/nm1304.


News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at niaid.nih .


Anne A. Oplinger

aoplingerniaid.nih

301-402-1663

NIH/National Institute of Allergy and Infectious Diseases

niaid.nih

Foot Fashion Could Ease Arthritic Knees

The use of special mobility shoes can help ease knee pain and slow disease progression in people with osteoarthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Atlanta.


Osteoarthritis, or OA as it is commonly called, is the most common joint disease affecting middle-age and older people. It is characterized by progressive damage to the joint cartilage the cushioning material at the end of long bones and causes changes in the structures around the joint. These changes can include fluid accumulation, bony overgrowth, and loosening and weakness of muscles and tendons, all of which may limit movement and cause pain and swelling.


"Forces on the knee joint during walking have been shown to be related to pain, severity and progression of knee osteoarthritis," explains Najia Shakoor, MD; associate professor of medicine at Rush University in Chicago and lead investigator in the study. "Therefore, researchers currently investigate strategies to reduce these forces or loads on the knee joint in hopes of preventing progression of the disease." Dr. Shakoor's study recently tested these strategies, more specifically, by studying how the use of mobility shoes flat and flexible shoes, created specifically for this research, that allow natural foot mobility and provide sufficient support for the foot can affect knee OA.


At the beginning of the study, researchers used a special camera system and a force plate to determine gait (how a person walks) in 16 participants (who were all diagnosed with knee OA through X-rays and based on symptoms) while they walked in their own shoes, in mobility shoes, and barefoot. After this initial evaluation, participants were instructed to wear the mobility shoes a minimum of six hours per day, six days a week for six months. To determine the progression of each participant, researchers performed the same gait analysis that was performed at the beginning of the study at six, 12 and 24 weeks.


Overall, researchers determined that mobility shoes, in comparison to conventional shoes, led to significantly decreased knee loads in the participants. Additionally, they found that longer-term use of the mobility shoes led to even better outcomes in participants noting a reduction in knee load that increased from 3.7 percent at the beginning of the study to 9.4 percent after six weeks, and to 18 percent at six months. Finally, researchers found that after 24 weeks of wearing mobility shoes, participants experienced an adaptation in their gait (with a knee load reduction of 11 percent) even when wearing conventional shoes leading researchers to believe that the use of mobility shoes could create beneficial neuromuscular and behavioral changes in how people with OA walk.


"This study showed that specialized footwear was beneficial in reducing knee loads substantially over six months," says Dr. Shakoor. "It is also the first study to show that chronic use of a mechanical, knee-load reducing intervention could lead to favorable alterations in the way participants walk even once the intervention is removed. "


Source: American College of Rheumatology (ACR)

Plexxikon Selects Clinipace Worldwide To Manage Four Clinical Trials

Clinipace Worldwide, a global digital clinical research organization (dCRO), announced that Plexxikon Inc., a leader in the structure-guided discovery and development of novel small molecule pharmaceuticals to treat human disease, has selected Clinipace to manage all aspects of four clinical trials comprising a Phase 1 healthy volunteer study, a Phase 1b rheumatoid arthritis (RA) study, and two phase 2 oncology studies.


Plexxikon announced in January that enrollment started for the first of two Phase 1 clinical trials with PLX5622, a novel, oral, targeted and highly selective Fms kinase inhibitor for the treatment of autoimmune diseases such as RA. The initial Phase 1 trial is a single-ascending dose (SAD) study in up to 48 healthy volunteers. The second trial is a multiple-ascending dose (MAD) study in approximately 32 RA patients that will begin once the first SAD healthy volunteer cohort has been cleared for safety, with continued enrollment in a staggered fashion following each SAD dose level. Both studies are being managed by Clinipace Worldwide.


Additionally, Plexxikon has awarded Clinipace Worldwide two phase 2 trials with PLX3397, an orally available compound that selectively co-inhibits three key kinase targets-Fms, Kit and FIt3-ITD-resulting in down-modulation of a number of cell types including macrophages, microglia, osteoclasts and mast cells, as well as cells harboring the Flt3-ITD mutation, a driver in as many as 30% of acute myeloid leukemia (AML) cases. These clinical trials are targeted for initiation in 2011 and focus on recurrent glioblastoma multiforme and relapsed or refractory Flt3-ITD+ AML.


"We chose Clinipace Worldwide to manage these important clinical trials for both PLX5622 and PLX3397 based on Clinipace's commitment to customer service. Plexxikon's programs are highly differentiated from its competition, and we needed a highly differentiated CRO to get the job done. The Clinipace team values each working opportunity as a true, strategic partnership," said Paul Lin, MD, MBA, Director of Business Development, Plexxikon. "We believe in Clinipace's dCRO model and the Clinipace team. As our portfolio grows in value, we have confidence that Clinipace has the experience and expertise to handle additional, mission-critical trials with high visibility and efficiency."


"As a digital CRO, we know that successful trials hinge on the transparent exchange of trial and project data among all constituents," said Jeff Williams, CEO, Clinipace Worldwide. "This platform enables our clients to substantially improve their ability to avoid problems and mitigate risk. As a result we look forward to a long-lasting and successful partnership with Plexxikon as they continue to bring innovative and effective drugs to market."


Source:

Plexxikon

Clinipace Worldwide

New 'Work Charter' Launched To Help 6.5m People With Musculoskeletal Conditions To Stay In Work, UK

Today the Arthritis and Musculoskeletal Alliance (ARMA), backed by leading policymakers and employers, is calling for positive action to ensure people with musculoskeletal disorders (MSDs) are properly supported to access employment and remain in their jobs.



Launching a new Charter for Work, ARMA is calling on policymakers, employers, and healthcare professionals to make a commitment to decrease the number of people who fall out of the workplace as a result of ill-health:



- MSDs are the second biggest cause of work-limiting health problems and sickness absence in the UK, responsible for up to 10.8 million lost working days in 2008/09


- The cost of MSDs to society has been estimated at over ??7 billion at 2007 prices


- Persistent pain and stiffness that MSDs can cause have a major impact on quality of life and can result in more days off work



The Charter contains a set of cohesive actions developed in partnership with NHS Employers, The Royal College of Nursing and The Work Foundation.



ARMA director, Ros Meek said,



"ARMA seeks to build on the progress made following Dame Carol Black's Review 'Working for a Healthier Tomorrow' - we want to capitalise on this work and drive positive action and behaviour change in our workplaces, local NHS and wider communities.



"We are urging all employers, both private and public sector, to show their commitment to the health of their workforce and adopt the Charter. By taking small steps they can help to transform the lives of people with MSDs and benefit their bottom line by retaining valuable skills."



The Charter outlines actions for policymakers, employers, healthcare professionals and patients themselves:



- Better flexible working arrangements and training of line managers


- The delivery of integrated services at a local level to ensure early diagnosis and treatment


- Ensuring an open dialogue between employers and employees to effectively manage a person's condition



Conservative Shadow Health Minister Anne Milton MP, commented:



"With musculoskeletal disorders affecting 6.5million people and costing society over ??7 billion a year, it is important that policymakers and employers take positive steps to ensure that those who can work are supported to do so. We need to rise to this challenge in order to help restore economic growth; and refocus on capacity rather than incapacity - which costs individuals and taxpayers dearly."



Karen Charman, Head of Employment Services at NHS Employers, said



"The NHS has been working for several years to reduce the impact of musculoskeletal disorders (MSDs) by improving the services available to affected staff and by encouraging better working practices with a view to eliminating the causes of these life altering conditions. NHS Employers are delighted to have been able to support ARMA in developing this Charter and hope that it will help all employers to understand and address the needs of affected employees."



Dr Peter Carter, Chief Executive & General Secretary of the RCN said:



"Nurses are often at a very high risk of developing musculoskeletal conditions, so it is vital that employers take preventative action and offer support where it is needed. This charter is useful for nurses in pushing for this commitment from employers, but it is also useful for those offering support to patients with such conditions, whose health and wellbeing can be improved by being able to stay in work".



Steve Bevan, Managing Director of The Work Foundation commented:



"The Work Foundation welcomes the launch of the Charter for Work and its objectives. Our research across Europe on MSDs shows that absence from work and lost productivity attributable to MSDs costs Europe over 240 billion Euros each year and that governments, clinicians and employers can do much more to help people with MSDs to stay in or return to work. For most people, good work is good for their health. We support any steps which allow people with long-term or chronic health conditions to play their full part in the labour market."



Source
Arthritis and Musculoskeletal Alliance

New Data Points To Long Lasting Beneficial Effects Of CEL-SCI's Rheumatoid Arthritis Vaccine

CEL-SCI Corporation (NYSE: CVM) announced the presentation of new rheumatoid arthritis data at the 6th annual GTCbio Vaccine Conference in Vienna, Va. The data, presented by Dr. Daniel Zimmerman, Senior Vice President of Research, Cellular Immunology of CEL-SCI, indicate that CEL-SCI's rheumatoid arthritis treatment vaccine CEL-2000 prevents or retards the permanent tissue damage caused by rheumatoid arthritis. The long term results obtained with CEL-2000 vaccine, for the rheumatoid arthritis, were in line with those seen with Enbrel(R), a leading treatment for people with rheumatoid arthritis.


CEL-2000 may also offer a number of potential advantages over existing rheumatoid arthritis treatments, such as Enbrel. Data collected in the animal studies conducted with CEL-2000 demonstrated that CEL-2000 is an effective treatment against arthritis even with the administration of fewer treatments. CEL-2000 is also potentially a more disease-type specific therapy, should be significantly less expensive and finally, CEL-2000 could also be useful for patients who are not able to take or who may be unresponsive to existing anti-arthritis therapies.


In these studies, mice were injected with collagen on days 0 and 21 to induce the disease. Once the mice cohorts reached a significant and uniform and measurable disease (arthritis) state, therapy with Enbrel or CEL-2000 was initiated and continued for 28 days. CEL-2000 was administered only twice and Enbrel was administered every other day for the first 28 days and an arthritic Index score was determined for both groups. The observation period was doubled from previous studies and was continued for another 28 days for a total study period of 56 days.


"It is very exciting to see the reduction of severe rheumatoid arthritis damage in these animals through a simple vaccination," said Dr. Zimmerman. "I am hopeful that CEL-2000 will one day be used to lessen the damage caused by rheumatoid arthritis in patients."


Rheumatoid arthritis treatments comprise a $13 billion market. Enbrel, a leading rheumatoid arthritis treatment sold by Amgen and Wyeth, reported US sales in 2007 of about $3.2 billion. Enbrel is a soluble recombinant protein of a human TNF-alpha receptor linked to human IgG Fc. In some cases, human or humanized monoclonal antibodies specific against TNF-alpha have also been used for therapy in rheumatoid arthritis. These therapies remove or inactivate TNF-alpha, a natural human cytokine required in many immune functions for normal defenses.


CEL-SCI's rheumatoid arthritis vaccine CEL-2000 was discovered as part of work with the Company's ongoing research and development activities with its L.E.A.P.S.(TM) (Ligand Epitope Antigen Presentation System) technology. L.E.A.P.S. is a novel T-cell modulation platform technology that enables CEL-SCI to design and synthesize proprietary immunogens. Any disease for which an antigenic sequence has been identified, such as infectious, parasitic, malignant or autoimmune diseases and allergies, are potential therapeutic or preventive sites for the application of L.E.A.P.S. technology.















The concept behind the L.E.A.P.S. technology is to directly mimic cell/cell interactions on the T-cell surface with synthetic peptides. The L.E.A.P.S. constructs containing the antigenic disease epitope linked to a T-cell binding ligand (TCBL) can be manufactured by peptide synthesis or by covalently linking the two peptides. Depending upon the type of L.E.A.P.S. construct and TCBL used, CEL-SCI is able to direct the outcome of the immune response towards the development of T-cell function with primarily effector T-cell functions (T Lymphocyte; helper/effector T lymphocyte, type 1 or 2 [Th1 or Th2], cytotoxic [Tc] or suppressor [Ts]). Therefore, it would appear that the L.E.A.P.S. construct represents a chimeric peptide with bi-functional behavior.


CEL-SCI Corporation is developing products that empower immune defenses. Its lead product is Multikine(R) which is being readied for a global Phase III trial. The Company has operations in Vienna, Virginia, and Baltimore, Maryland. CEL-SCI's other products, which are currently in pre-clinical stage, have shown protection against a number of diseases in animal tests and are being tested against diseases associated with bio-defense and avian flu.
When used in this report, the words "intends," "believes," "anticipated" and "expects" and similar expressions are intended to identify forward-looking statements. Such statements are subject to risks and uncertainties which could cause actual results to differ materially from those projected. Factors that could cause or contribute to such differences include, an inability to duplicate the clinical results demonstrated in clinical studies, timely development of any potential products that can be shown to be safe and effective, receiving necessary regulatory approvals, difficulties in manufacturing any of the Company's potential products, inability to raise the necessary capital and the risk factors set forth from time to time in CEL-SCI Corporation's SEC filings, including but not limited to its report on Form 10- K for the year ended September 30, 2007. The Company undertakes no obligation to publicly release the result of any revision to these forward-looking statements which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.


CEL-SCI Corporation

cel-sci



View drug information on Enbrel.

Medication For Juvenile Rheumatoid Arthritis Confirmed Effective By Study

Juvenile rheumatoid arthritis (JRA) is a chronic autoimmune disease that strikes children between the ages of newborn to 16 years. All children with JRA have joint pain, stiffness, and swelling and some also have fever and skin rashes. JRA can impede growth, damage joints, and lead to disability in adulthood. Traditionally, children with JRA have been treated with the same drugs prescribed to adults with inflammatory diseases: corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and disease-modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX). Unfortunately, these medications fail to improve disease activity for many children with JRA.



Tumor necrosis factor (TNF) plays a key role in the inflammatory process. In the past decade, TNF-blockers have brought dramatic gains in treatment for rheumatoid arthritis patients. Etanercept, the only FDA-approved biologic for JRA patients until very recently, has also been proven highly effective and safe for children in short-term trials. Yet, since many children with JRA have active disease that lasts for many years, past adolescence and into adult life for many, assurance of the effectiveness and safety of long-term anti-TNF treatment is essential.



Toward that goal, the Pediatric Rheumatology Collaborative Study Group - comprised of over 70 pediatric rheumatology centers in the US and Canada has been conducting a trial of etanercept in JRA patients for more than 8 years. The group shares reassuring news for pediatricians, parents, and, above all, children afflicted with JRA in the May 2008 issue of Arthritis & Rheumatism.



To evaluate the long-term therapeutic value of etanercept, the study group began with a randomized controlled trial, focusing on 69 JRA patients between the ages of 4 and 17 years. Treatment with MTX and other DMARDs was discontinued a minimum of 2 weeks before enrollment, while maintaining a low-dose regimen of corticosteroids or NSAIDs was allowed. Patients received injections of etanercept based on the patient's body weight with a maximum weekly dosage of 50 milligrams. As the trial was extended beyond 1 year, participants were permitted to add low-dose MTX if recommended by their physician. At every 3 months during the first year of the extension phase, and then every 4 to 6 months during the following years, participants were assessed for improvement in overall disease status using the American College of Rheumatology Pediatric (ACR Pedi) criteria, as well as evaluated for changes in joint inflammation, mobility, pain, ability to perform routine daily tasks and C-reactive protein level. Patients were also monitored for frequency of serious adverse events (SAEs) such as those that required hospitalization, resulted in prolonged incapacity or death. Also medically important infections (MIIs) defined as those that required treatment with intravenous antibiotics were monitored.
















58 JRA patients, 84 percent of the participants in the randomized controlled trial, enrolled in the long-term extension trial and received weekly treatment for a total of 318 patient years of etanercept exposure. Most patients were female (67 percent) and white (74 percent), and all had taken MTX prior to the study. At baseline, the mean age of the patients was 10 years and the mean duration of disease was 5.9 years. 42 of these patients (72 percent) entered the fourth year of continuous etanercept treatment, and 26 patients (45 percent) entered the eighth year. Here's an overview of the results:
16 of the original 69 study participants reported 39 serious adverse events, for an overall exposure-adjusted rate of 0.12 SAEs per patient year. This rate did not increase with long-term exposure to etanercept.


8 patients reported 9 medically important infections over the course of the long-term trial, for an overall exposure-adjusted rate of 0.03 MIIs per patient year. This rate did not increase with long-term exposure to etanercept.


The most common adverse event was a flare of JRA. There were no reported cases of tuberculosis, which has been linked to anti-TNF therapy, or lupus; no malignancies or lymphomas; no nervous system disorders; and no deaths.


Among patients who received 8 years worth of weekly etanercept treatment, 100 percent achieved an ACR Pedi 70 response, indicating 70 percent improvement in joint symptoms from baseline. Over the course of the study, only 7 patients withdrew due to the therapy's lack of effectiveness on disease activity.

"Continuous treatment with etanercept resulted in truly important, often profound, sustained improvement in all aspects of this disease including clinically important signs and symptoms of JRA, improvements in functional ability and decreased pain for up to 8 years," notes study group spokesperson Dr. Daniel J. Lovell. Demonstrating long-term safety comparable to studies of patients across a variety of rheumatic disorders, this study supports the potential of etanercept therapy to give children with JRA the promise of a better quality of life as adults.







Article: "Safety and Efficacy of up to Eight Years of Continuous Etanercept Therapy in Patients with Juvenile Rheumatoid Arthritis," Daniel J. Lovell, Andreas Reiff, Norman T. Ilowite, Carol A. Wallace, Yun Chon, Shao-Lee Lin, Scott W. Baumgartner, and Edward H. Giannini, for the Pediatric Rheumatology Collaborative Study Group, Arthritis & Rheumatism, May 2008; 58:5 pp. 1496-1504.



Source: Sean Wagner


Wiley-Blackwell

Genetic Pathway Responsible For Link Between Body Clock Disturbance And Worsening Arthritis

The genes that regulate human circadian rhythm, or 'the body clock', are significantly disturbed in individuals with arthritis, according to the results of a new study presented at EULAR 2009, the Annual Congress of the European League Against Rheumatism in Copenhagen, Denmark. Notably, a specific genetic pathway has been identified as responsible for interactions between the genes that regulate the body clock and those that may worsen symptoms of arthritis.



In a sample of 200 rheumatoid arthritis (RA) patients, sleep was determined to be significantly disturbed in over 61%, as determined by a Pittsburg Sleep Quality Index (PSQI) score of >5 (the PSQI global score was 8.55 ?±4.69). These values were shown to correlate with several measures of arthritis disease activity, including levels of c-reactive protein, swollen joint count and DAS28*.



A further element of the study looked into the expression patterns of certain genes in mice with arthritis. Here, researchers identified a novel biochemical pathway in which the circadian regulatory gene CRY was found to up-regulate expression of a gene which promotes the activation of TNF-alpha (tumour necrosis factor-alpha, a pro-inflammatory cytokine used by the body to boost the immune system) by two fold, when comparing mice with the CRY gene removed to those with a normal copy of the gene.



Professor Shunichi Shiozawa of Kobe University Graduate School of Medicine and University Hospital, Japan, who led the research said: "Our study has shown that arthritis interferes with the genetics behind an individual's circadian rhythm and, specifically, that certain body clock genes may play a part in the activation of TNF-alpha, a signaling molecule that has an important role in the inflammation commonly seen in a number of rheumatologic conditions. The identification of this curious pathway may help to explain the 24-hour symptom cycle seen by many patients who experience worsening of joint pain and stiffness in the mornings, and lead to further research into new approaches for improving daily quality of life."



RA patients who participated in the study were attending the Kakogawa Konan Hospital and Kobe University Hospitals. Experimental arthritis was induced in mice with the CRY gene removed. Expression of the genes responsible for regulation of the human body clock were determined by immunohistochemistry and quantitative Polymerase Chain Reaction. TNF-alpha levels were measured by ELISA, and transactivation of TNF-alpha gene was examined by reporter assay.



* DAS28 (Disease Activity Score) is an index used by physicians to measure how active an individual's RA is. It assesses number of tender and swollen joints (out of a total of 28), the erythrocyte sedimentation rate (ESR, a blood marker of inflammation), and the patient's 'global assessment of global health'. A higher score indicates more active disease.



Abstract number: AB0084



Source:
Rory Berrie


European League Against Rheumatism

Materials Scientists From Jena University Fight Arthrosis And Osteoporosis: Cartilage Comeback

At some point it catches up with everyone. With increasing age joints and bones wear out. When for instance the cartilage, functioning as cushions between the joints becomes worn out, in most cases only the surgeon implanting a replacement part helps. Until now at least. Scientists of the german Jena University - together with colleagues from France, England, Germany and Switzerland - are working on a tiny device that is being implanted in the joint and is supposed to trigger the regeneration of cartilage produced naturally in the body. The project OPHIS (Composite Phenotypic Triggers for Bone and Cartilage Repair) is subsidized with 4 Million Euro from the EU, of which 350.000 go to the Jena University. The project is running for four years.



Mostly Arthrosis and Arthritis patients will be able to profit by the results of the project, as the regeneration of the cartilage can be reactivated on smaller lacerations when the doctor recognizes the illnesses early enough. "Even though there are products like this on the market," says Prof Dr Frank M??ller, Materials Scientist of the Jena University. "None of them adheres actively with the bone underneath. This is exactly the improvement of our implant."



The cellulose implant, of one centimeter diameter, is sponge-like and has two different surfaces. "The implant can substantially adhere to the bone through inorganic activation with calcium phosphate-nanoparticles on its lower surface," explains the Jena Professor for Science and Technology of Surfaces and Interfaces.



"Scientists of another sub-project in Brighton in England apply growth factors on the opposite, porous surface of the implant to trigger the regeneration and ingrowth of cartilage cells." Materials scientists of Jena University are able to produce the required porous surfaces with an especially developed process via ice templating. "For that purpose vegetal cellulose is being dissolved in water containing solvent and then deep-frozen at a defined speed," says Prof M??ller. "The ice crystals are so grown at a controllable temperature gradient. Afterwards the cellulose is being freeze-dried, so that little holes - pores - take the place of the ice cristals, as the water is being changed from a solid to a gaseous aggregate state. So a micro porous surface is created according to a given specification." A facility especially for this process had been constructed in Jena.



Apart from cellulose implants composites from cellulose and collagen are being tested. These are even more promising, as the structural protein collagen is an important organic part of the connective tissue and thereby also of the bone and cartilage.



Moreover the scientists of the research project are aiming to fighting osteoporosis. Again tiny implants are supposed to stop the bone loss and to trigger the bone growth. These implants constist of bacterial cellulose, which is developed in co-operation with the research group of Dr Dana Kralisch at the Institute for Technical Chemistry and Environmental Chemistry at the Jena University. "Certain bacterial strains use glucose in their culture medium to produce cellulose," the project manager of Jena University explains. "When you influence the production by a shaking movement of the fluid, small pellets will form. These structures which are porous by nature are provided with defined protein sequences - so-called peptides - and are implanted into the bone. Bone forming cells migrate and the bone growth is re-stimulated."



Source:

Axel Burchardt

Friedrich-Schiller-Universit?¤t Jena

MayoClinic, Adds Three New Centers Focusing On Osteoporosis, Rheumatoid Arthritis And Osteoarthritis

MayoClinic , an award-winning consumer health information site, has added three new centers focusing on osteoporosis, rheumatoid arthritis and osteoarthritis. The new areas provide visitors with detailed, easy-to-find information on symptoms, tests, diagnosis and complications associated with these conditions.


Osteoporosis Center


Osteoporosis is a disease in which bones become fragile and more likely to break. If not prevented or if left untreated, it can progress painlessly until a bone breaks. These fractures occur typically in the hip, spine and wrist.


The new Osteoporosis Center on MayoClinic provides users with treatment information, plus background on symptoms, prevention and risk factors.


Osteoporosis is a major public health threat, potentially affecting 55 percent of Americans over 50. While it is often thought of as an older person's disease, it can strike at any age. In the United States, an estimated 10 million people (20 percent of them men) already have the disease and nearly 34 million more have low bone mass, increasing their risk for osteoporosis.


Rheumatoid Arthritis Center


The nagging pains and physical limitations of the more than 100 forms of arthritis are common to millions of people. Rheumatoid arthritis is among the most debilitating of all forms, mainly characterized by inflammation of the lining, or synovium, of the joints. It can lead to long-term joint damage, resulting in chronic pain, loss of function and disability.


The new Rheumatoid Arthritis Center on MayoClinic provides users with information on rheumatoid arthritis treatment, plus details on symptoms, tests, diagnosis and complications.


About 2 million people in the United States, approximately 1 percent, have rheumatoid arthritis. It can affect anyone, including children, but 70 percent of people who have the disease are women. Onset usually occurs between 30 and 50 years of age.


Treatments for arthritis have improved in recent years. Most involve medications. But in some cases, surgery may be necessary.


There is no cure for rheumatoid arthritis. But with proper treatment, a strategy for joint protection and changes in lifestyle, patients can live long, productive lives.















Osteoarthritis Center


Osteoarthritis is the most common type of arthritis, and occurs most often as people age. Sometimes it's called degenerative joint disease or osteoarthrosis.


The new Osteoarthritis Center on MayoClinic provides visitors with information on osteoarthritis treatment and symptoms. The site also discusses diagnosis and the disease's complications.


Nearly 21 million Americans over age 25 have osteoarthritis. Although it's more common in older people, younger people can develop it -- usually as the result of a joint injury, a joint malformation, or a genetic defect in joint cartilage. Before age 45, more men than women have osteoarthritis; after age 45, it is more common in women. It's also more likely to occur in people who are overweight or who have jobs that put stress particular joints.


There's no cure for osteoarthritis, but available treatments can relieve pain and help individuals remain active.


About MayoClinic


Launched in 1995 and now visited by nearly 10 million users a month, this award-winning Web site offers health information, self-improvement, and disease management tools to empower people to manage their health. Produced by a team of Web professionals and medical experts, MayoClinic gives users access to the experience and knowledge of the more than 2,000 physicians and scientists of Mayo Clinic. MayoClinic offers intuitive, easy-to-use tools such as "Symptom Checker" and "First-Aid Guide" for fast answers about health conditions ranging from common to complex; as well as more in-depth sections on over 25 common diseases and conditions, healthy living articles, videos, animations and features such as "Ask a Specialist" and "Drug Watch." Users can sign up for a free weekly e-newsletter called "Housecall" which provides the latest health information from Mayo Clinic. For more information, visit mayoclinic.

New Risk Factor Gene For Rheumatoid Arthritis Identified By Researchers

Scientists at The Feinstein Institute for Medical Research and a team of collaborators from across the country have identified a new risk factor gene for rheumatoid arthritis. The paper will be published in Nature Genetics and the finding brings light to the nature of the disease. The gene, dubbed REL, is a member of the NF-??B family, important transcription factors that have many roles in the body. The NF-??B family seems to have a big hand in regulating the body's immune response as well.



"The NF-??B is a key switching point for many cellular activities," said Peter K. Gregersen, MD, head of the Robert S. Boas Center for Genomics and Human Genetics at the Feinstein Institute and lead author of the study. Dr. Gregersen is part of a nationwide consortium of investigators seeking to identify risk genes for rheumatoid arthritis (RA). The hope is to figure out the genetic triggers and identify treatments that block this autoimmune process. In theory, such advances can point the way to understanding other autoimmune disorders. About one percent of the population will develop rheumatoid arthritis, which can be crippling.



REL is a key regulator of CD40, which works through the NF-??B pathway.



"This paper represents the latest in a series of important publications chronicling an exceptionally productive collaboration between extramural and intramural scientists through the North American Rheumatoid Arthritis Consortium," said Daniel Kastner, MD, PhD, clinical director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. "In describing yet another gene in the CD40 signaling pathway that is involved in rheumatoid arthritis susceptibility, this paper reinforces the possibility of targeting this pathway in selected patients with this debilitating illness."



The consortium has helped identify many genes involved in rheumatoid arthritis but this genetic finding is significant because of its key role in immune system regulation. It did not reveal itself in previous genetic studies because the sample size was just not large enough. In previous studies, genetic samples from about 2,000 patients were used to identify markers associated with risk for RA. In the latest study, the scientists analyzed samples from 4,000 RA patients and controls.



According to Dr. Gregersen, this particular genetic variant is rather common, found in about a third of people in North America. That means that it must confer an important survival advantage. That said, scientists need to figure out its role in increasing the risk for RA. Next on the research agenda is to see if they can measure how the gene is regulated under specific conditions that set the stage for RA. "There are a huge number of unknowns," said Dr. Gregersen. "These findings are clear - this pathway is involved - but there is a lot of work to be done."



Genetic differences between individuals help scientists understand many diseases. But this is just the beginning, added Dr. Gregersen. Today, most markers that are used to identify genes represent variants that occur in more than five percent of the population. The next wave in genetic screening will have to include the variants that occur in less than one percent of the population.



Notes:

In addition to the Feinstein Institute, part of the North Shore-LIJ Health System, other centers that are part of the RA consortium include: the University of Texas, MD Anderson Cancer Center; the Genetics and Genomics Branch of the National Institute of Arthritis, Musculoskeletal and Skin Diseases; the Rowe Program in Genetics, University of California at Davis; the Russell Medical Research Center for Arthritis, Department of Medicine, University of California, San Francisco; Brigham and Women's Hospital at Harvard Medical School; University of Colorado Denver School of Medicine; University of Nebraska Medical Center; Central Hospital in Finland; University of Pittsburgh Medical Center; University of Alabama at Birmingham; Mount Sinai Hospital; University Health Network in Ontario, Canada; and Celera.

The work was supported by grants from the US National Institutes of Health NO1-AR-2-2263 (P.K.G.), RO1 AR44422 (P.K.G.) and by the Eileen Ludwig Greenland Center for Rheumatoid Arthritis and the Muriel Fusfeld Foundation. The work was also supported in part by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and by grants from the Canadian Institutes for Health Research (MOP79321) and Ontario Research Fund (RE01061) and a Canada Research Chair to K.A.S.



Source:
Jamie Talan


North Shore-Long Island Jewish (LIJ) Health System

Medarex Announces Primary Endpoint Achieved In MDX-1100 Anti-IP-10 Antibody Phase 2 Trial For Rheumatoid Arthritis

Medarex, Inc. (Nasdaq: MEDX) announced that the MDX-1100 Phase 2 proof-of-concept trial in patients with active rheumatoid arthritis (RA) receiving methotrexate successfully met its primary endpoint. The top-line results from the recently completed 70-patient multi-center, randomized, double-blind, placebo-controlled Phase 2 trial indicated that when compared to placebo, three times the number of patients treated with 10 mg/kg of MDX-1100 every two weeks achieved at least a 20% improvement in RA signs and symptoms at 12 weeks, the primary endpoint of the study, as measured by the American College of Rheumatology (ACR) 20 measurement of response. These results were statistically significant when compared with placebo (p=0.0024). The antibody combination with methotrexate was generally safe and well-tolerated. Full results from this Phase 2 trial are planned to be presented at a future scientific meeting.


"We are greatly encouraged by this demonstration of efficacy from a well-designed and well-executed study," said Howard H. Pien, Chairman and CEO of Medarex. "These results show that by targeting the chemokine IP-10 with our MDX-1100 antibody, we may be able to offer a potentially important and novel treatment option for rheumatoid arthritis and potentially other inflammatory indications."


"Based on these positive results with a novel pro-inflammatory target, we are actively preparing for the next stage of clinical development for MDX-1100 in RA, including the potential for subcutaneous dosing," said Geoffrey M. Nichol, M.B.Ch.B., Senior Vice President of Product Development at Medarex. "We also look forward to exploring the broader potential of MDX-1100 in a range of inflammatory diseases, including ulcerative colitis in an ongoing companion Phase 2 study."


About MDX-1100 in Rheumatoid Arthritis


MDX-1100 is a fully human antibody that targets IP-10 (also known as CXCL-10), a chemokine expressed in association with multiple inflammatory disease indications. The MDX-1100 Phase 2 study in RA enrolled 70 patients with active disease while on methotrexate. Patients in the study were randomized to receive either placebo or MDX-1100 (10 mg/kg) every two weeks for a total of six doses. The primary endpoint of the study was ACR20 response at 12 weeks. Secondary endpoints included other clinical response assessments, pharmacokinetics of MDX-1100, and potential biomarkers of activity.


According to the American College of Rheumatology, 1.3 million adult Americans have been diagnosed with rheumatoid arthritis, a chronic autoimmune disease that develops when certain cells of the immune system inappropriately attack healthy joint tissue, thereby causing swelling, inflammation and damage of joints, as well as systemic inflammation and damage of other tissues.


About MDX-1100 in Other Indications


MDX-1100 is also being explored as a treatment for ulcerative colitis (UC). A Phase 2 randomized, double-blind, placebo-controlled study in patients with active UC while continuing standard UC therapy is ongoing. The Phase 2 trial is expected to enroll up to 106 patients at multiple centers internationally. Patients in the study are randomized to receive either placebo or MDX-1100 (10 mg/kg) every two weeks for a total of four doses. The primary endpoint of the study is response rate at 8 weeks. Clinical response is based on the Mayo score, a composite endpoint that assesses stool frequency and the amount of bloody stool per day as recorded in a patient diary, physician global assessment and the assessment of colon mucosal inflammation ascertained by endoscopy.















Ulcerative colitis is a chronic inflammatory bowel disease characterized by inflammation and ulceration of the lining of the colon. Symptoms typically include bloody diarrhea and abdominal pain and in severe cases may require colectomy. According to the Crohn's & Colitis Foundation of America, it is estimated that there are up to approximately 500,000 Americans with ulcerative colitis.


About Medarex


Medarex is a biopharmaceutical company focused on the discovery, development and potential commercialization of fully human antibody-based therapeutics to treat life-threatening and debilitating diseases, including cancer, inflammation, autoimmune disorders and infectious diseases. Medarex applies its UltiMAb(R) technology and product development and clinical manufacturing experience to generate, support and potentially commercialize a broad range of fully human antibody product candidates for itself and its partners. Over forty of these therapeutic product candidates derived from Medarex technology are in human clinical testing or have had INDs submitted for such trials, with the most advanced product candidates currently in Phase 3 clinical trials, the subject of regulatory applications for marketing authorization or approved for commercial sale. Medarex is committed to building value by developing a diverse pipeline of antibody products to address the world's unmet healthcare needs.


Medarex(R), the Medarex logo, UltiMAb(R) and HuMAb(TM) are trademarks of Medarex, Inc. All rights are reserved.


Source: Medarex, Inc

NIAMS Funds New Centers Of Research Translation

NIAMS Funds New Centers of Research Translation Bridging the gap between bench and bedside is the goal of four new Centers of Research Translation (CORTs) funded by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), part of the National Institutes of Health (NIH). CORTs are designed to bring together basic and clinical research in a way that helps translate basic discoveries into new drugs, treatments and diagnostics.



The four new centers are:



Center for Translating Molecular Signal Pathways to Orthopaedic Trauma Care, headed by Randy Rosier, M.D., Ph.D., chair of orthopaedics at the University of Rochester, N.Y. This center will study the biological basis of fracture healing and the efficacy of a potential new treatment, teriparatide, an injectable form of human parathyroid hormone that stimulates new bone formation.



Center for Lupus Research, headed by M. Virginia Pascual, M.D., at the Baylor Research Institute in Dallas, Texas. This CORT will study the role of different cell types in the origin and development of lupus, will develop markers of disease activity and severity, and will look for new targets for treatment. Lupus is an autoimmune disease that can affect many parts of the body, including the joints, skin, kidneys, lungs, heart and/or brain.



Center for X-Linked Hypophosphatemic Rickets Research, led by Thomas O. Carpenter, M.D., at Yale University in New Haven, Conn. This center will study the various molecular contributors to this genetic form of rickets and work toward developing new treatments.



Center for Research Translation in Scleroderma, headed by Frank Arnett, M.D., professor of internal medicine in the Division of Rheumatology at the University of Texas Medical School at Houston. This center will study the molecular basis of scleroderma to understand its underlying causes using functional genomics and gene networks. Studies will involve a multiethnic cohort of scleroderma patients, as well as two mouse models of fibrosis recently developed at this center. Scleroderma involves the abnormal growth of connective tissue, which supports the skin and internal organs.



CORT grants are a new funding mechanism for NIAMS, and require centers to encompass at least three projects, including one clinical and one basic research study.






The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, visit the NIAMS Web site at niams.nih/.



The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.



Contact: Ray Fleming


NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

Smoking and the risk of rheumatoid arthritis

Rheumatoid arthritis (RA), like many chronic diseases of the immune system, likely results from a combination of genetic
susceptibility and environmental triggers. Recently, a team of researchers in Sweden set out to investigate the interaction
of two specific risk factors: the presence of a gene encoding protein sequence called the shared epitope (SE), the major
genetic risk factor so far defined for RA, and cigarette smoking. The results, published in the October 2004 issue of
Arthritis & Rheumatism (interscience.wiley/journal/arthritis), indicate that smoking significantly increases
the risk of RA among men and women with a genetic predisposition for the disease.


Conducted by a research team in Sweden, this population-based study focused on a large sample of patients with a confirmed
diagnosis of the disease--858 individuals, 612 women and 246 men, with an average age of 49 years. The researchers also
recruited 1,048 healthy individuals to serve as controls. Participants donated blood samples for DNA genotyping. Every
participant also completed lifestyle questionnaires, including smoking habits. Since former smokers tend to have a wide
variation in their cumulative smoking history, the researchers chose to restrict their analysis to current smokers and men
and women who had never smoked.


The DNA samples of the RA patients were studied for evidence of genes for the SE. The SE is a protein sequence found in cell
surface molecules that regulate specific immune responses. The blood samples were also tested for rheumatoid factor, a
hallmark of this disease. Then, analyzing women and men together, the researchers compared current smokers with never smokers
for the risk of rheumatoid factor positive RA.


For people with the SE gene who never smoked, the increased risk for RA was assessed at 2.8 times. For current cigarette
smokers without the SE gene, the risk factor was comparable--2.4 times. These findings affirm the SE gene and smoking as
independently related to the development of rheumatoid factor positive RA. Among current smokers with the SE gene, however,
the disease risk increased to 7.5 times. "The interaction was even more pronounced in smoking subjects with double SE genes,
whose relative risk of rheumatoid factor positive RA was 15.7 times higher," observes one of the authors Leonid Padyukov,
M.D., Ph.D. However, no risk was found for rheumatoid factor negative RA in this study.


Beyond strengthening the case against cigarette smoking as a health hazard, this study has important implications for ongoing
research into the factors contributing to RA and other autoimmune diseases. "Our study also emphasizes the need to include
data on environmental exposures in genetic analyses of a complex disease," the authors note.


Article: "A Gene-Environment Interaction Between Smoking and Shared Epitope Genes in HLA-DR Provides a High Risk of
Seropositive Rheumatoid Arthritis," Leonid Padyukov, Camilla Silva, Patrik Stolt, Lars Alfredsson, and Lars Klareskog for the
Epidemiological Investigation of Rheumatoid Arthritis Study Group, Arthritis & Rheumatism, October 2004; 50:10; pp.
3085-3092.


Contact: Amy Molnar

amolnarwiley

John Wiley & Sons, Inc