According to the results of two phase III clinical trials to be presented this week at the annual meeting of the American College of Rheumatology (ACR), the investigational biologic abatacept (ab-a-'ta-sept) demonstrated significant clinical activity in patients with rheumatoid arthritis. The medication, referred to as a potential first-in-class T-cell costimulation modulator, was discovered and developed by Bristol-Myers Squibb Company.
 
The studies focused on two different rheumatoid arthritis patient populations: either those who had not adequately responded to methotrexate or patients who did not adequately respond to tumour necrosis factor (TNF) inhibitors. As assessed by clinical measures, including disease progression, ACR response rate, physical function and quality of life, patients in both studies given abatacept in addition to therapy such as methotrexate showed improvements compared to those receiving placebo plus additional therapy.
 
The researchers explain that activated T cells in the body orchestrate the autoimmune response that leads to the joint inflammation and destruction as well as the disability often associated with rheumatoid arthritis. Abatacept selectively modulates one of the two signals needed for full T cell activation, thereby interrupting the inflammatory process. A primary endpoint in each study was the proportion of patients achieving an ACR 20 response at six months, which is a way of determining patient improvement by examining multiple measures of disease activity. Patients recording an ACR 20 response have at least a 20 percent improvement in signs and symptoms of rheumatoid arthritis.

One trial, referred to as AIM (Abatacept in Inadequate Responders to Methotrexate), assessed efficacy and safety of abatacept for a period of 12 months in rheumatoid arthritis patients who inadequately responded to treatment with methotrexate. Through one year of abatacept treatment, 73.1% of patients on abatacept achieved an ACR 20 response compared to 39.7% on placebo. ACR 50 and ACR 70 responses in the abatacept group at one year (48.3% and 28.8%, respectively) exceeded what was observed in the placebo group (18.2% and 6.1%, respectively). The incidence of adverse events was slightly higher with abatacept compared to placebo (87% vs. 84%, respectively).

Abatacept had a low incidence of infusion reactions and serious infections, such as pneumonia, (3.9% for abatacept vs. 2.3% for placebo). The most common adverse events in the trial were headache, nasopharyngitis and nausea.
 
"The responses seen with abatacept increased through one year of treatment," said Joel Kremer, M.D., Director of Research at The Center for Rheumatology in Albany, N.Y. "These data confirm results from earlier studies and provide evidence for the potential benefit of targeting T-cell activation in rheumatoid arthritis treatment."
 
A second trial, referred to as ATTAIN (Abatacept Trial in Treatment of Anti-TNF Inadequate Responders), evaluated efficacy and safety of abatacept for a period of six months in patients with active rheumatoid arthritis and inadequate response to TNF inhibitors. Patients randomized in the trial had discontinued all TNF therapy. In addition to at least one DMARD, patients received abatacept at a fixed dose approximating 10 mg/kg (258 patients) or a placebo (133 patients). After six months of treatment, 50.4% of the patients on abatacept achieved ACR 20 responses compared to 19.5% on placebo. Additionally, 20.3% of patients in the abatacept group achieved ACR 50 and 10.2% achieved ACR 70. By contrast, 3.8% of the placebo group achieved ACR 50 and 1.5% reached ACR 70.

According to a team of researchers in Sweden, rheumatoid arthritis (RA), like many chronic diseases of the immune system, likely results from a combination of genetic susceptibility and environmental triggers. The team 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, 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.

October 12th - 20th marks the fourth annual Bone and Joint Decade (BJD) Action Week, dedicating specific days to major conditions affecting the musculoskeletal
system, with activities aimed at highlighting the significant impact of these disorders on millions of children, adults and elderly people worldwide. Focus days include:

• October 12 - World Arthritis Day
• October 14 – BJD Communications Day
• October 16 - World Spine Day
• October 17 - World Trauma Day
• October 20 - World Osteoporosis Day

This year’s Action Week is highlighted by activities around the world -- the following is a sample of international and country-specific activities:
 
Action Week Webcast Series: As part of its internet-based education series, the Decade invites members of the public to log on to its Action Week Webcast Series, to view online presentations from key opinion-leaders in musculoskeletal health on topics such as Osteoporosis, Low-Back Pain, Road Traffic Injury Prevention, and so on. Each educational eLecture runs for 30 minutes and is freely accessible via the following link: http://www.boneandjointdecade.org/AW/
 
Croatia: The Croatian Network has organised a week-long programme of special symposia, expert meetings, and lectures, bringing together leaders from Dubrava University, the Croatian National League Against Rheumatism, Zagreb Hospital, the Croatian Ministry of Home Affairs, the Croatian Rheumatoid Society, Croatian Association for Osteoporosis, Croatian Gerontology Society, to name just a few. Many events will be open to the public.
 
Switzerland: As part of a special collaboration between the Swiss Bone and Joint Decade Network and the Swiss Arthritis Association, World Arthritis Day 2004 marks the launch of a nation-wide awareness campaign focussing on avoiding arthritis disability through early intervention.
 
Thailand: A celebrity-hosted Bone and Joint Decade Walk & Run Mini-Marathon will trace the streets of Bangkok on Sunday, October 17th, as a part of the grand celebration of the 6th cycle birthday (72nd birthday anniversary) of Her Majesty Queen Sirikit, the Queen of Thailand. See www.boneandjointdecade.or.th.
 
United States: At the American Stock Exchange in New York City, Joe Klecko, a former player with the New York Jets, and Gary Whyte, an advocate for increased research into musculoskeletal health, will ring the opening bell in honour of the Bone and Joint Decade's Awareness Week. Charlene Waldman of the Paget Foundation, Drs. Adele Boskey and Cathleen Raggio of the Hospital for Special Surgery in New York, will also be among those present on behalf of the Decade. In addition, the American Academy of Orthopaedic Surgeons is developing three radio spots for release during Awareness Week. Last year, the Academy’s releases reached an estimated 26 million Americans. For other news on US Awareness Week activities, visit www.usbjd.org.
 
Launched in January 2000, the Bone and Joint Decade is an NGO, headquartered in Sweden, comprised of National Action Networks in more than 50 countries and with the support of more than 750 related organisations worldwide. Its mission is to advance understanding of musculoskeletal disorders worldwide through research and to improve the quality of life for those affected by these disorders. The Bone and Joint Decade is supported by National Action Networks, professional medical societies, patient advocacy groups, governments, industry and researchers who are to effect change. The Bone and Joint Decade is delighted to have the personal and active support of Kofi Annan, Secretary-General at the UN, the WHO and the World Bank. 

The Canadian Rheumatology Association (CRA) has issued a statement to its 350 members and other interested parties, recommending alternative treatment considerations in the wake of the worldwide recall of Merck’s rofecoxib, (Vioxx) last week.
 
“With millions of Canadians being affected by the Vioxx withdrawal, we believe it is important to provide their health professionals with important considerations when prescribing alternatives,” explained CRA President Michel Zummer, MD, FRCPC. The statement has been posted on the CRA web site (www.cra-scr.ca) and has been issued to medical and pharmacy associations across the country.
 
The CRA statement recommends that all patients taking Vioxx, a cyclooxygenase II selective inhibitor (Coxib), discontinue its use and contact their prescribing physician about an alternative, which may include another coxib or non-steroidal anti-inflammatory (NSAID) medication. It also urges physicians and pharmacists to make all possible efforts to arrange for their patients to discontinue Vioxx.
 
While there is no published evidence as to ideal alternative treatments, the CRA urges health professionals to consider the following when making a decision to switch their patient to another analgesic, such as a NSAID or another coxib:

1. There is no data to date that other NSAIDs or coxibs have caused cardiovascular problems similar to Vioxx. Pfizer conducted a similar prospective randomized controlled trial with high dose celecoxib vs. placebo and did not report an increase in myocardial infarctions.
2. NSAIDs which are primarily COX I-selective, such as ibuprofen and indomethacin, could interfere with the effectiveness of aspirin in preventing arterial thrombotic events. NSAIDs which are more COX II-selective (diclofenac, etodolac, nabumetone, meloxicam) are less likely to have this interaction.
3. Patients should be evaluated for their risk of an arterial thrombotic event (stroke, MI) when making a decision as to which alternative NSAID or coxib to use. 
4. Patients should also be evaluated for their risk of gastrointestinal (GI) ulceration and bleeding and more importantly other illnesses that could result in the inability to tolerate  this. These patients will require a Proton Pump Inhibitor (esomeprazole, lansoprazole, omeprazole, pantoprazole) in conjunction with their NSAID, or treatment with a more selective Coxib, or in some cases a topical NSAID.
5. Both celecoxib and valdecoxib are relatively contraindicated in patients with sulpha allergies.

Rheumatologists, as specialists in the branch of internal medicine that deals with diseases of the joints, connective tissues of the body, and illnesses that are rheumatic in nature, are experts in arthritis care. The CRA represents 350 Canadian rheumatologists and promotes their pursuit of excellence in arthritis care and research in Canada through leadership, education and communication.  

On September 30, 2004, Merck &. Co., Inc. announced a voluntary worldwide withdrawal of PrVIOXX (rofecoxib). In a news release issued today, Merck Frosst reiterated that it will reimburse all Canadian patients for their unused tablets of VIOXX.
 
The procedure for reimbursement is as follows:

1. Patients may return their unused tablets to the pharmacist from whom they purchased their prescription.
2. The patient will be reimbursed by the pharmacist for the amount of unused tablets they return.
3. The amount of the patient's reimbursement will be based on what the patient paid at the time they filled the prescription.
4. Please note that all reimbursement requests and the return of the product must be completed by November 30, 2004.

Patients are asked not to flush unused tablets down the toilet or sink to avoid contaminating ground or municipal water systems. Returning the unused tablets to the pharmacy will not only ensure that patients are reimbursed, but that the medication will be disposed of safely.
 
More information about the reimbursement policy can be found on www.merckfrosst.com or by calling the Customer Information Centre at 1-800-567-2594. 

The Arthritis Society encourages patients who are currently taking VIOXX® to contact their doctor to discuss discontinuing the use of VIOXX, and possible alternative medications.

The Arthritis Society continues to focus on the health and well being of the four million Canadians who live with arthritis. The announcement by Merck & Co., Inc. to voluntarily withdraw VIOXX will certainly be of concern to those patients who are currently taking this particular medication to relieve the symptoms of their arthritis.

The side effects of VIOXX, as is the case with many other medications, need to be considered by patients, and their doctors, based on individual needs – and risk factors – of each patient. Fortunately, there are other medications, ones that are not affected by the decision today, that are still available to people living with arthritis. 

“Merck Frosst deserves credit for making what must have been a very difficult decision corporately,” said John Fleming, the CEO of The Arthritis Society. “This is a decision that has clearly been made with the best interests of patients in mind.” Fleming went on to say that, “Merck Frosst has been a strong supporter of the work of The Arthritis Society, particularly with regards to increasing awareness about this painful and debilitating disease.
 
Merck Frosst Canada has advised The Arthritis Society that it will reimburse patients for unused VIOXX tablets. More information will be posted on their Web site in the next few days. Patients may obtain information from Merck Frosst Canada by calling 1-800-567-2594 or going to www.merckfrosst.ca. 

Merck &. Co., Inc. today announced a voluntary worldwide withdrawal of VIOXX (rofecoxib), its arthritis and acute pain medication. The company's decision, which is effective immediately, is based on new, three-year data from a prospective, randomized, placebo-controlled clinical trial, the APPROVe (Adenomatous Polyp Prevention on VIOXX) trial.
 
The trial, which is being stopped, was designed to evaluate the efficacy of VIOXX 25 mg in preventing recurrence of colorectal polyps in patients with a history of colorectal adenomas.  In this study, there was an increased relative risk for confirmed cardiovascular events, such as heart attack and stroke, beginning after 18 months of treatment in the patients taking VIOXX compared to those taking placebo.  The results for the first 18 months of the APPROVe study did not show any increased risk of confirmed cardiovascular events on VIOXX, and in this respect, are similar to the results of two placebo-controlled studies described in the current U.S. labeling for VIOXX.
 
"We are taking this action because we believe it best serves the interests of patients," said Raymond V. Gilmartin, chairman, president and chief executive officer of Merck.  "Although we believe it would have been possible to continue to market VIOXX with labeling that would incorporate these new data, given the availability of alternative therapies, and the questions raised by the data, we concluded that a voluntary withdrawal is the responsible course to take."
 
APPROVe was a multi-center, randomized, placebo-controlled, double-blind study to determine the effect of 156 weeks (three years) of treatment with VIOXX on the recurrence of  neoplastic polyps of the large bowel in patients with a history of colorectal adenoma. The trial enrolled 2,600 patients and compared VIOXX 25 mg to placebo. The trial began enrollment in 2000.  
 
VIOXX was launched in the United States in 1999 and has been marketed in more than 80 countries. In some countries, the product is marketed under the trademark CEOXX.
 
Results of the VIGOR (VIOXX Gastrointestinal Outcomes Research) study, released in March 2000, demonstrated that the risk of gastrointestinal toxicity with VIOXX was less than with naproxen, but indicated an increased risk of cardiovascular events versus naproxen.  However, in other studies including Merck's Phase III studies that were the basis of regulatory approval of the product, there was not an increased risk of cardiovascular events with VIOXX compared with placebo or VIOXX compared with other non-naproxen non-steroidal anti-inflammatory drugs (NSAIDs). Merck began long-term randomized clinical trials to provide an even more comprehensive picture of the cardiovascular safety profile of VIOXX.
 
"Merck has always believed that prospective, randomized, controlled clinical trials are the best way to evaluate the safety of medicines. APPROVe is precisely this type of study - and it has provided us with new data on the cardiovascular profile of VIOXX," said Peter S. Kim, Ph.D., president of Merck Research Laboratories. "While the cause of these results is uncertain at this time, they suggest an increased risk of confirmed cardiovascular events beginning after 18 months of continuous therapy. While we recognize that VIOXX benefited many patients, we believe this action is appropriate."
 
Merck has informed the U.S. Food and Drug Administration and regulatory authorities in other countries of its decision. The company also is in the process of notifying health care practitioners in the United States and other countries where VIOXX is marketed. Patients who are currently taking VIOXX should contact their health care providers to discuss discontinuing use of VIOXX and possible alternative treatments. In addition, patients and health care professionals may obtain information from www.merck.com and www.vioxx.com.

With the release of the ICES Report on Arthritis in Ontario yesterday, The Arthritis Society is warning of a looming healthcare crisis for people affected by arthritis and their families.
 
“The number of people with arthritis has increased in only seven short years by 23% to over 1.6 million Ontarians,” reports Jo-Anne Sobie, Executive Director, The Arthritis Society, Ontario Division. “In the next 20 years that number of people with arthritis in Ontario will increase to 2.8 million. That’s staggering - more than 1 in 5 of us – but it doesn’t begin to measure the devastating impact that arthritis can have on people’s lives. Arthritis is the most frequently reported cause of pain and disability.”
 
Jo-Anne Sobie adds that people don’t take arthritis seriously. “They are told that arthritis is a natural part of aging, and they should just live with it. That’s simply untrue. The end stage of arthritis is already causing significant wait times for joint replacement surgery.” The demand for hip and knee replacement surgery has been increasing rapidly over the last decade. With the aging baby boomer population and the current level of arthritis, the demand for joint replacement surgery will mushroom over the next few years.
 
The ICES Research Atlas: Arthritis and related conditions in Ontario shows:

• Over 1.6 million people are living with the daily pain and disability of arthritis in Ontario. This represents a 17.5% prevalence rate in the Ontario’s population.
• In 2000, there were 8.9 half-day rheumatology clinics per week per 100,000 people in Ontario. 
• Between 1997 and 2000, there has been no growth in the number of clinics available to people with arthritis.
• In 2000, there were 22 half-days of office and surgery time per 100,000 people in Ontario.
• Between 1997 and 2000, there was a decrease of 2.3 half-days available to people with arthritis and other Ontarians requiring orthopedic care.

“But this represents only the tip of the iceberg”, says Dr. Elizabeth Badley, ICES Senior Adjunct Scientist and lead author of the 2004 ICES Research Atlas: Arthritis and Related Conditions in Ontario. According to the ICES Atlas, “The general level of services in Ontario provided for people with arthritis has remained fairly static since 1997. As the number of people with arthritis increases, this translates into declining levels of service per individual and likely has implications for health care providers’ ability to provide adequate care.”
 
“People with arthritis are not getting the care they need to manage their disease and minimize the pain and disability it causes,” adds Jo-Anne Sobie of The Arthritis Society. 

Great strides have been made in arthritis research and there are now many effective treatments available.  Most specialists now consider inflammatory arthritis (including Rheumatoid Arthritis (RA), Psoriatic Arthritis, Spondylitis, and Scleroderma) to be a medical emergency. It needs to be diagnosed and treated early to reduce joint damage.
 
“We need to let people know they should take arthritis seriously, and encourage them to seek help to reduce the impact of the disease,” says Sobie. “They need improved access to diagnosis, disease information, self-management education, specialist care, rehabilitation and drugs to reduce pain and disability.”
 
The Arthritis Society is calling on the Ontario government to develop a province-wide strategy to improve access to programs and services for the prevention and management of arthritis. It has created a 12-point agenda to improve access to arthritis care for all Ontarians, and is asking the government to include arthritis as a priority on its chronic disease management agenda in order to reduce wait times for joint replacement surgery. 

Click here for the complete release.

A genetically engineered 'mighty mouse' is helping Medical College of Georgia researchers find the best way for young people to build bone and avoid osteoporosis.

"We are interested in kids; we want to know how to maximize their bone during peak periods of growth while they still can," says Dr. Mark Hamrick, bone biologist. "One of the best predictors of who is going to get osteoporosis and who is not is how much bone you have at sexual maturity. So we want to know what people can do from zero to age 18 that really is going to pack that bone on." These mighty mice, with up to 70 percent more muscle mass than a regular mouse and essentially no body fat, and a $1 million grant from the U.S. National Institutes of Health are helping Dr. Hamrick answer that question. The mice lack the myostatin gene, a negative regulator of muscle mass. "Lots of genes control muscle development," says Dr. Hamrick. "This one is pretty significant in terms of not letting muscles get too big."

Myostatin is expressed at highest levels during development, when the embryo is growing, to ensure that muscles don't overgrow, Dr. Hamrick says. The level expressed changes naturally over the course of life. "It's still expressed as children grow and is present in very low levels in adults," he says. "It's suggested that you might get rises in myostatin levels with aging, which is associated with a loss of muscle mass that typically accompanies increased age. " Some muscle-wasting diseases as well as space flight and extended bed rest also are associated with increased myostatin levels. Numerous products claim to help adults build muscle by turning off this powerful muscle regulator produced by muscle cells, Dr. Hamrick says. But the only product scientifically proven to block myostatin is a monoclonal antibody now under study for its potential to treat muscular dystrophy, he says.

The muscular rodents that result when myostatin is taken out of the equation are enabling scientists to explore the hypothesis that one of the best ways to build bone is to build muscle.

"People have argued for many years that the way to increase bone density and strength is force - bones respond to the stress and strain placed on them by forming more bone - and the best way to increase that force is big muscles," says Dr. Hamrick. "We want to know if that is the case. We want to know if certain genes involved in bone formation are up-regulated with increased muscle and if these genes are stress-responsive genes.

"We also want to know if muscle can affect bone in other ways. Maybe it affects different hormones. Maybe it's a source of different growth factors itself. There's the frequency of a stimulus, not just the magnitude of it. There are also changes in blood and fluid flow that occur. We need to know the real mechanism."

Like many age-related infirmities, osteoporosis is becoming a bigger concern as people live longer, he says. Weak, fracture-prone bones likely are in the future for many children who today appear polar opposites: those too fat from overeating and inactivity or too frail from not eating because of an obsession with thinness, says the scientist and father.

By combining stem cell science with orthopedic surgery, a team of researchers at the University of  British Columbia and Vancouver Coastal Health Research Institute aims to reduce the 10 per cent failure rate in hip replacements and make repeat replacements and other joint repairs obsolete within 10-15 years.

With $1.5 million over five years in funding from the Canadian Institutes for Health Research, a group of seven UBC scientists will explore how stem cells - the body's "master cells" that can reproduce and develop many mature functional cells - can be used to regenerate bone cells to better secure artificial joints and other bone replacement structures. "We're very excited about the potential for long-term success for patients who need repeat surgery to repair or replace bone," says Fabio Rossi, UBC assistant professor of medical genetics and Canada Research Chair in Regenerative Medicine. "By using a well-understood stem cell and available technologies, we can accelerate research and have our discoveries quickly incorporated into patient care."

The team will create a new fixative mixture that combines minerals and slow-release growth factors. The mixture will be seeded with the patient's own mesenchymal stem cells - a type of stem cell that is easily extracted from adult bone marrow and capable of manufacturing bone cells and connective tissue. This "living glue" will form a strong, organic environment to secure artificial joints, vertebrae or other replacement structures where the original replacement has failed.

"Currently, these repeat replacements are difficult because considerable bone is lost as the joint gradually breaks down," says team member Tom Oxland, Canada Research Chair in Biomedical Engineering and director of The Centre for Hip Health, located at the Vancouver Coastal Health Research Institute (VCHRI). "New techniques will fill a critical need for the increasing number of people undergoing hip replacement and will also be useful for other bone loss patients." Hip fracture is one of the most common problems leading to bone loss and currently there is a 10 per cent failure rate in the 20,000 hip replacements performed annually in Canada. Problems include breakdown of the acrylic glue used to secure the prosthetic joint and weakened or damaged tissue surrounding the joint.

Team members include Don Brunette, associate dean, Research, Faculty of Dentistry; Pharmaceutical Sciences Prof. Helen Burt; Orthopedics Dept. Head Clive Duncan; Applied Science Assistant Prof. Goran Fernlund and Orthopedics Engineering post-doctoral fellow Hanspeter Frei. 

In preparation of the upcoming first ministers’ summit on health, The Arthritis Society has put Prime Minister Paul Martin and all 13 of Canada’s premiers on notice that it will be issuing an annual report card on access to care and treatment for people with arthritis. 

In a letter to the first ministers, John Fleming the CEO of The Arthritis Society said, “Please know that Canadians with arthritis intend to judge the results and outcomes of your work with your colleagues.” Fleming added, “September is Arthritis Awareness Month, an auspicious time for these talks.”

In one year’s time, The Arthritis Society will conduct a survey of its patients, volunteers, health care providers, donors and researchers. The results will then be turned into The Society’s first report card on access to care and treatment for people with arthritis. According to Fleming, “This debilitating disease costs the Canadian economy $4.4 billion per year. With improved access to care and treatment, many of the health care and lost productivity costs associated with arthritis can be reduced.”

With the number of people affected expected to increase from four to six million people over the next twenty years, the demands of people with arthritis will be an important issue for the health care system. As new medications and joint replacement surgery are expected to be at the forefront of treatment options, the system will be under significant pressure. According to Fleming, “By improving access to care and treatment, many of the people who would otherwise have to endure the pain, fatigue and physical limitations associated with this disease, will be able to remain in the work force and lead a normal life.”   
 
The criteria that will be used to evaluate the health care system will be based on the Canadian Arthritis Bill of Rights. It was developed through the efforts of key players in the arthritis community, including advocates, rheumatologists, orthopedic surgeons, therapists and other health care professionals. First unveiled in January 2002, the Bill of Rights sets out the basic rights and responsibilities for Canadian arthritis patients.

Linda Wilhelm has lived with severe rheumatoid arthritis for 20 years.  She feels especially strong about using a report card to evaluate the impact of changes to the health care system. “The Bill of Rights recognizes the importance of accelerating access to new medications that give people back their lives.” She went on to explain that, “Health Canada needs to approve drugs more quickly and provincial governments need to help pay for them.” The latest, advanced arthritis medications used to treat moderate to severe arthritis can cost upwards of $20,000 per year. 

“The needs and interests of patients have to be at the forefront of our leaders’ minds.” says Ann Qualman, President of the Canadian Arthritis Patients Alliance. “People with arthritis must be at the table to work with government once an accord is struck. I know we join with many other patient groups in making this demand.” As an active volunteer who already contributes a significant amount of time to arthritis issues, Qualman says she is ready to go to work as soon as a deal is struck.

Click here for the complete release.

The September issue of Nature Immunology reports that researchers at Roche Basel (Switzerland) in collaboration with immunologists at the Harvard Medical School (Boston, Massachusetts) have discovered a naturally occurring peptide that could play a pivotal role in the fight against autoimmune diseases.
 
According to a release by Roche Pharmaceuticals, the so called CLIP (class II associated invariant chain peptide) peptide lowers the production of those cells of the immune system that are critical in triggering pro-inflammatory immune responses, including autoimmunity. This finding may give rise to new therapeutic strategies in particular in the field of rheumatoid arthritis (RA).
 
"RA belongs to the group of autoimmune diseases that depend on the expansion of a subset of blood cells -- so called helper T lymphocytes (TH1)", explained Harald Kropshofer, Ph.D., Roche Head Non-clinical Immunology. "Particular TH1 cells contribute to autoimmunity by recognizing proteins of our own body, thereby triggering adverse reactions of the immune system against the body's own tissues. At a certain stage, these TH1 cells begin to secrete hormone-like substances, such as interferon-gamma (IFN-gamma), interleukin-2 (IL-2) or interleukin-6 (IL-6), that can trigger, mediate and maintain autoimmune diseases. Hence, a peptide that helps to lower the generation rate or abundance of these TH1 cells could be an extremely helpful approach in RA therapy."
 
Kropshofer's team, along with one led by Anne Vogt, Ph.D., Head Applied Immunology, Roche Center for Medical Genomics, showed in a series of preclinical studies that specialized cells of the immune system, termed 'dendritic cells', turn on the natural occurring peptide CLIP on the cell surface which reduces the number of helper T cells changing to the TH1 type. Thus, CLIP appeared to function as a novel type of peptide regulator. More important, the researchers found that synthetic CLIP had the same function as naturally occurring  CLIP. This opens up the possibility of using synthetic CLIP or variants thereof as therapeutic agents. CLIP mediates its activity by binding to molecules of the major histocompatibility complex (MHC) class II which are being viewed as risk factors for RA and other autoimmune diseases. "The potential pharmacological importance of this discovery comes from the fact that modulating levels of CLIP may be used to modulate the immune response itself," said Ira Mellman, Department Head Ludwig Institute of Cancer Research, Yale University, New Haven. 

According to researchers at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, they've identified a novel disease mechanism underlying rheumatoid arthritis that may open the door to new therapies for this and other autoimmune disorders.

In an article appearing in the September 1 issue of the Journal of Immunology, principal investigator Dr. Terry J. Smith describes research that identifies an interaction between antibodies found in patients with rheumatoid arthritis and the insulin-like growth factor receptor (IGF-1R) as a cause of inflammation and lymphocyte infiltration. Dr.Smith published similar results last year dealing with Graves' disease, an autoimmune disorder affecting the thyroid gland and eyes.
 
Dr. Smith and his colleagues found that specific immunoglobins "turn on" the IGF-1R much like IGF-1 itself is known to do. Once the receptor is "on", a number of molecular events occur, including the production of two very powerful factors known to trigger T lymphocytes and direct them to sites of inflammation. In addition, the researchers found that blocking the interaction between the antibodies and IGF-1R arrests the progression of molecular events leading to T cell activation.
 
According to Dr. Smith, "It is possible that these findings will allow us for the first time to interrupt the disease process before any lasting damage occurs." Rheumatoid arthritis is one of several autoimmune disorders in which cellular defense mechanisms identify the body's own tissues as foreign and seek to destroy them. Other autoimmune disorders include such ailments as Graves' disease, multiple sclerosis and lupus. This research suggests that there could be a common therapeutic strategy for these conditions.
 
According to Kenneth P. Trevett, JD, President and CEO of LA BioMed, "The research by Dr. Smith offers the promise of a magic bullet treatment for several autoimmune diseases." 

A University of Iowa (UI) team has engineered a mouse that provides new insights into the virus. The animal model has implications for advancing treatments for patients with AIDS or an organ transplant who get a certain type of cancer, and for people with immune system diseases such as lupus, arthritis and multiple sclerosis. The study results appear in the August issue of the journal Immunity.

The advance builds on previous UI studies done in cell culture and provides researchers with a model that allows them to see biological functions related to Epstein-Barr within the context of a whole organism, said Gail Bishop, Ph.D., Distinguished Professor of Microbiology and Internal Medicine in the UI Roy J. and Lucille A. Carver College of Medicine and a research career scientist with the Department of Veterans Affairs (VA) Iowa City Health Care System.

"Mice cannot be infected with Epstein-Barr because they do not have the receptor for this virus. What we have done is express in the mouse the most important transforming protein that is involved in the virus in humans," said Bishop, who also is associate director for basic science research at the Holden Comprehensive Cancer Center at the UI.

The Epstein-Barr virus, a member of the of herpes virus family, infects most people by adulthood, then remains latent (inactivated) after an initial and usually symptomless infection. People who get the virus in their teens or early 20s may get mononucleosis. But for people with AIDS or who are on immunosuppressive drugs to prevent rejection of a donated organ, there is a risk that the activated virus will produce a viral protein called latent membrane protein 1 (LMP1), which in turn can cause B cell lymphoma, or tumors, Bishop said.

The new mouse model will help researchers study how LMP1 impacts specific organs or tissues. Previous UI studies helped show that this viral protein mimics a normal cellular process in humans. In that process, a protein called CD40 signals B cells (white blood cells) to divide and make antibodies against infection, then terminates the signal when the need for the immune response is gone. LMP1 also triggers B cell activation, but in contrast to CD40, fails to stop it at the appropriate time.

"The viral protein is an amazing mimic of the normal protein but, in a way, the viral protein does its functions too well," Bishop said. "The viral protein causes abnormal survival and activation of these B cells." Lymph nodes all over the bodies of these mice are enlarged by excess B cells. In addition, there is increased production by the B cells of antibodies against normal cellular components. These antibodies are called auto-antibodies.

"In humans, these auto-antibodies work against components of one's own body and are seen in other autoimmune diseases such as lupus, arthritis, diabetes and multiple sclerosis," Bishop explained. The researchers found that mice with LMP1 made excess auto-antibodies. This means that the mice could serve as a model for understanding how to prevent this overproduction in humans, with implications for not only Epstein-Barr Virus but also autoimmune diseases.

In addition to Bishop, major collaborators on the projects included the two lead authors Laura Stunz, Ph.D., UI associate research scientist, and Lisa Busch, a UI doctoral candidate in molecular biology who has since graduated.