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Multiple Sclerosis Foundation Internet Newsletter

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APRIL 2006 - MSFYi

"Courage is being scared to death and saddling up anyway."
- John Wayne

In This Issue:

TESTOSTERONE MAY HELP MEN WITH MS

* MORE EVIDENCE FOUND LINKING EPSTEIN-BARR & MS
* OLIGOCLONAL BAND TEST PREDICTS CONVERSION TO MS
* ENROLLMENT BEGINS FOR COMBINATION CLINICAL TRIAL
* CORRELATION BETWEEN LESION LOAD & AXONAL LOSS
* ROCKY MOUNTAIN MS CENTERS ANNOUNCES NEW FORUM
* SATIVEX RESULTS DISAPPOINTING
* DOUBLE-DOSING COPAXONE®
* NEW REBIF® FORMULATION SUBMITTED IN USA & EUROPE

MSF News:
* NUTRITION & MS BOOKLET AVAILABLE
* MSF CELEBRATES 20 YEARS!
* MSF LAUNCHES SPANISH HELPLINE
* NEED TO TALK? VISIT OUR MSFAMILIES FORUM!

TESTOSTERONE MAY HELP MEN WITH MS

According to researchers at the University of California, Los Angeles, early testosterone therapy may help improve cognitive function and slow brain atrophy in men with MS. Testosterone, the principal male sex hormone which is secreted in the testes of men and the ovaries of women, may help protect nerve cells from damage caused by the type of autoimmune system attack that occurs in MS.

This study included 10 men with relapsing-remitting MS who were not taking an immunomodulating drug. For one year, all participants received daily treatment with 100 milligrams of a testosterone gel applied to the skin. They were assessed at three-month intervals.

After 12 months, the men showed significant improvements on a test that measured brain processing speed and working memory. There were also signs of improvement in tests of spatial memory (i.e., where objects are and how they relate to other objects in space, both physically or geographically). During the last nine months of testosterone treatment, the rate of brain atrophy slowed by 67 percent. Blood tests showed that production of a chemical called brain-derived neurotrophic factor, which helps promote nerve cell survival, increased more than twofold after testosterone treatment.

No change in the number or size of lesions as measured by MRI was noted, although lesion activity was low in the group overall. Further study using a placebo-controlled, blinded design is needed to confirm these preliminary findings. These findings were presented at the American Academy of Neurology's annual meeting in San Diego, California.

"This research is interesting," comments Ben Thrower, M.D., Medical Director of the MS Center at Shepherd. "Men without MS who have low testosterone levels usually feel significantly better when the problem is treated. The slowing of the rate of atrophy is encouraging but must be duplicated with a control group. There is always a chance that the slowing of any observed MRI measure (atrophy, enhancing lesions, or new T2 lesions) could represent natural history and not treatment effect. Of course, when we see clinical improvement as well, like the changes on cognition in this study, it becomes less likely that we are seeing natural history alone. In women, testosterone has sometimes been used as a therapy for low libido. At higher doses, side effects might include increased risk for cardiovascular disease and the development of abnormal masculine characteristics."

According to a study that will appear in the June 2006 issue of the Archives of Neurology, young adults with high levels of antibodies against the Epstein-Barr virus may be more likely to develop MS 15 to 20 years later.

Epstein-Barr virus (EBV), a member of the herpesvirus family, is one of the most common human viruses and the virus that most often causes mononucleosis. EBV occurs worldwide, and most people become infected with EBV sometime during their lives.

Researchers have long suspected that external factors may influence the risk for MS. Some studies have suggested that the Epstein-Barr virus, which according to the Centers for Disease Control and Prevention, affects up to 95 percent of adults by the time they reach age 35 to 40, may play a role.

Researchers at Kaiser Permanente in Oakland, California, examined the records of patients who joined a health plan between 1965 and 1974, when they were an average of 32.4 years old. The patients had undergone multiple examinations, answered questions about their health and behaviors and submitted blood samples, which were processed and stored at cold temperatures.

Between 1995 and 1999, researchers searched medical records maintained by the health plan and selected 42 individuals with MS who had blood samples in storage collected prior to their diagnosis. Two controls for each case were then matched to each MS patient by age, sex, and date of blood collection. The blood samples of all participants were then analyzed to determine the levels of antibodies against the Epstein-Barr virus. Measuring antibodies (which are proteins produced by the body to fight infection) is one method of determining exposure to or presence of a particular virus in a person's body.

The 36 women and six men who developed MS had their first symptoms at an average age of 45 and an average of 15 years after their blood was collected. The average concentration of anti-Epstein-Barr virus antibodies was significantly higher among individuals who had developed MS than among those who hadn't. Those with four times the level of antibodies were approximately twice as likely to develop MS. Researchers reported that the elevated levels became evident between 15 and 20 years before patients first experienced the neurological symptoms of MS and remained elevated afterwards.

While researchers don't understand how the Epstein-Barr virus causes the body to attack its own central nervous system, mounting evidence is showing a relationship between the Epstein-Barr virus infection and other autoimmune diseases, particularly systemic lupus.

Understanding the mechanisms that link Epstein-Barr virus infection to MS and other autoimmune diseases could eventually result in new ways to treat and prevent these diseases.

Individuals with a clinically isolated demyelinating syndrome (CIS) are at risk of developing a second attack, thus converting into clinically definite MS. Therefore, an accurate prognostic marker for that conversion might allow early treatment.

Brain MRI and oligoclonal IgG band (OCBG) detection are the most frequent paraclinical tests used in MS diagnosis. Researchers from Hospital Ramon y Cajal in Madrid, Spain, found that a new OCBG test has shown high sensitivity and specificity in differential diagnosis of MS.

To evaluate the accuracy of the new OCGB method and of current MRI criteria to predict conversion of CIS to definite MS, 52 patients with CIS were studied with OCBG detection and brain MRI and followed up for 6 years. The sensitivity and specificity of both methods to predict conversion were analyzed.

OCGB detection showed a sensitivity of 91.4% and specificity of 94.1%. Current MRI criteria had a sensitivity of 74.23% and specificity of 88.2%. The presence of either OCGB or MRI criteria studied simultaneously showed a sensitivity of 97.1% and specificity of 88.2%.

Researchers concluded that the presence of oligoclonal IgG bands is highly specific and sensitive for early prediction of conversion to MS and that simultaneous use of both tests shows high sensitivity and specificity.

"Early diagnosis of MS remains an important goal," comments Ben Thrower, M.D. "Many studies have shown that nerve fiber (axonal) damage occurs early in the course of the disease. Early initiation of therapy will depend upon early diagnosis. About a year ago, the FDA approved the OCGB test used in this study. An older version of CSF testing was likely less sensitive."

Enrollment has begun for CombiRx, a clinical trial that will determine if the combined use of Avonex® (interferon beta-1a) once a week and Copaxone® (glatiramer acetate) daily is a more effective treatment than either treatment alone.

Approximately 130,000 MS patients are already receiving either Avonex or Copaxone. For the study, 50 percent of participants will receive both medications; 25 percent will receive Avonex with a daily placebo; and the remaining 25 percent will receive Copaxone with a weekly placebo. No participants will receive just a placebo.

Because Avonex and Copaxone affect MS by different mechanisms, the use of the two drugs in combination seemed sensible to researchers.

Enrollment for the study is underway at clinics across the United States and Canada. For more information, call (866) 848-3088.

Traditionally, researchers have believed that MS is a demyelinating disease and that lesion load plays a major role in disease progression. Interest has increased regarding the presence of axonal loss. The relative roles of demyelination and axonal loss in MS, or their possible correlation, have not been fully clarified.

U.K. researchers stained for myelin post-mortem material from the cerebrum, brainstem and spinal cord of 55 MS patients. Age range was between 25-83 years and the length of disease history ranged from 2 to 43 years. Lesion load was calculated by determining the relative proportion of lesion area compared with total white matter area of the corticospinal and sensory tracts at each level. This was related to estimates of axonal density and the total axon number in these tracts in the spinal cord.

Results indicate that lesion load did not correlate with brain weight. Unexpectedly, after modifying for sex, age and disease history, correlations between total lesion load and axonal loss, in both the corticospinal tract and sensory tracts, were weak or absent at each level investigated.

Since little correlation between lesion load and axonal loss was found, the possibility that demyelination is not the primary determinant of spinal cord axonal loss warrants further consideration.

"This study confirms what others have shown. There is a lot more to MS than just white spots on an MRI," explains Ben Thrower, M.D. "Disability in MS is really a reflection of tissue damage in the brain and spinal cord. The number and/or volume of white matter lesions do not correlate well with tissue damage or disability. As more advanced technology becomes available, we may have better insight into what really goes on in the central nervous system in MS."

ROCKY MOUNTAIN MS CENTERS ANNOUNCES NEW FORUM

The Rocky Mountain MS Center has announced a new service for its registered users. This forum will provide access to a number of MS experts. This new service has been made possible, in part, through a grant from the MSF.

The forum's experts include Pat Daily, LCSW, Allen Bowling, M.D., Ph.D., Thomas Stewart, M.S., J.D., PA-C, and Pat Kennedy, RN, ANP. Each has years of experience, across a broad range of topics, in counseling patients with MS. Questions should be directed to "Pat." She will answer or refer questions, as needed.

To learn more, please visit http://www.mscenter.org/forum. In order to participate, you must log in. Your username and password are both the same - your full email address, including the @ symbol.

The mission of the Rocky Mountain Multiple Sclerosis Center is to help people living with MS and their families lead a quality life by providing individualized care, support, education and research.

GW Pharmaceuticals reported disappointing results from a final-stage trial of Sativex, its innovative cannabis-based medicine.

MS patients with spasticity who used the under-the-tongue spray and followed the trial's protocols did benefit. But an "intention to treat" analysis of all study patients found no statistically significant advantage compared with placebo.

"The concept of 'intention to treat' in a trial means that all patients selected for the study are included in the analysis, even if they dropped out," said Dr. T. Jock Murray of the Dalhousie MS Research Unit in Nova Scotia, Canada. "It often changes the results when compared to analysis of only those who successfully completed the trial."

GW may now delay filing for regulatory approval of the product in Europe.

It is likely that the company will now wait for results of other Phase III studies assessing Sativex for the relief of neuropathic pain in MS, where the most consistently positive data has been previously noted.

In Britain, approval was initially expected by 2003. But Sativex has experienced numerous delays, with regulators requesting more data to prove its benefits. In April 2005, Canada became the first country to approve the sale of Sativex as a treatment for neuropathic pain.

According to GW, its cannabis plants are grown under computer-controlled conditions in secure glasshouses at a secret location in the UK.

At the 58th Annual Meeting of the American Academy of Neurology, Teva announced that a new, higher dose of Copaxone (glatiramer acetate injection) showed promising results in the treatment of those with relapsing-remitting MS.

A 9-month, randomized, double-blind, parallel-group Phase II study of 90 patients compared a 40 mg dose of Copaxone to the currently approved 20 mg dose. A 38% greater reduction in mean cumulative number of gadolinium-enhancing lesions as measured by brain MRI was noted.

Those taking the double-dose of Copaxone experienced a reduced mean on-trial relapse rate of 77% when compared to annual relapse rate prior to entry, as compared to 62% with Copaxone 20 mg.

This study demonstrated that Copaxone 40 mg was well tolerated, with a safety profile similar to the currently available 20 mg dose.

A Phase III study, designed to further substantiate the higher efficacy of the increased dose of Copaxone, is in the planning stages.

The most common side effects of Copaxone are redness, pain, swelling, itching, or a lump at the site of injection, weakness, infection, pain, nausea, joint pain, anxiety, and muscle stiffness.

"I would not be surprised if injection site reactions were more frequent at the higher dose," said Ben Thrower, M.D. "Unless the double-dose was FDA approved, there will not be insurance coverage, so who knows what the cost might be. We have similar data on a double-dose of Betaseron®, with similar issues of side effects and cost."

Serono, co-marketers of Rebif, have submitted a supplemental Biological License Application (sBLA) to the U.S. Food and Drug Administration (FDA) and a variation to the current Marketing Authorization to the European Medicines Agency (EMEA) for a new formulation of Rebif (interferon beta-1a) as a treatment for MS.

Data from a Phase III clinical trial in those with relapsing forms of MS show the new formulation of Rebif results in a substantial improvement in overall tolerability, as measured by pre-specified parameters including injection site reactions. The data also show that the incidence of antibody formation with the new formulation is reduced.

"Hopefully, the new formulation will make users' lives a little bit easier. The slightly acidic pH of the current version will be corrected to make injection sites less painful," says Ben Thrower, M.D. "Anything that can be done to make injectable MS therapies less of a hassle should increase the likelihood of people staying on therapy over time."

The new formulation of Rebif is the latest of several product enhancements, including the Rebiject II autoinjector, a 29 gauge-needle pre-filled syringe, and a titration pack designed to make starting therapy easier and more convenient. Rebif, which is a three-times weekly subcutaneous injection, can be stored at room temperature for up to 30 days if a refrigerator is not available.

MSF NEWS

Eating consistently well over a period of time may help reduce fatigue, improve bladder and bowel problems, increase energy, and prevent bone loss. It may also positively impact mental and emotional health, including memory and concentration.

Although diet is not currently considered a causative factor in MS, there is anecdotal evidence from individuals with MS who have experienced health benefits by changing their diet. Whether you are interested in losing weight, gaining weight, learning about specific dietary regimes, or improving your overall health status, talk to your doctor and order your copy of Nutrition & MS - because the best decisions are informed decisions.

Call 888-MSFOCUS (673-6287) or send an email to support@msfocus.org and request your copy today.

2006 marks the 20th anniversary of the MSF! Just one of the ways in which we are commemorating this landmark year is by presenting a special monthly feature on our website. The feature for April is Twenty MSF Healthcare Volunteers: Who They Are and Why They Help. To read more, visit http://www.msfocus.org/twentieth.html. Next month, we'll highlight Twenty Leaders in MS.

The MSF is excited to announce the availability of a new toll-free helpline for Spanish-speaking individuals. The number is 1-800-448-4727.

Are you a friend, family member, care partner, or significant other of someone living with MS? Log onto our MSFamilies forum and talk to others facing similar challenges. Ask questions, offer support, meet new friends, or just vent among peers who understand where you're coming from.

Log onto our website at http://www.msfocus.org. Click on "forums" on the left-hand side of the home page, and click on MSFamilies. Don't need support? Maybe someone needs yours!

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**Editor's Note: The intent of this newsletter is to provide information on various medical conditions, medications, treatments, and procedures for your personal knowledge and to keep you informed of current health-related issues. It is not intended to be complete or exhaustive, nor is it a substitute for the advice of your physician. Should you or your family members have any specific medical problem, seek medical care promptly.

For questions regarding this publication, email editor@msfocus.org

For support services, email support@msfocus.org

Please do not reply to this email address for correspondence.