RESEARCHERS UNRAVELING GENETICS OF MS
Medical researchers have made significant progress in understanding the genetics involved in MS. In two new studies, published in the July 29th online edition of the New England Journal of Medicine and Nature Genetics, three teams of researchers say they have identified, by separate methods, new genetic variants that contribute to the disease.

MS is a disease in which the body's immune system mistakenly attacks myelin. For years, the cause of MS has been considered part genetic and part environmental. Trying to identify the genes involved, however, has proven frustrating. Consequently, researchers have been speculating about what genes might be involved and then seeing if individuals with MS have abnormal variants of that gene. In recent years, researchers have suspected more than 100 candidate genes, none of which could be confirmed, except for variations in the immune system that have been known about for some time.

One team used a new, advanced method called Whole Genome Association. The other teams used the candidate gene approach. Because all three teams identified the same gene, the researchers are confident they have opened a new avenue into the cause and possible treatment of MS.

The identified gene produces a substance called the interleukin-7 receptor, a protein that allows immune system cells to respond to a control agent. Researchers believe the receptor is part of a biochemical pathway involving many genes. Defects in any of these genes may lead to MS. Researchers now believe it is possible to explore the pathway and perhaps develop treatments to remedy the disease-causing process.

The new research is the result of several large teams at universities in the U.S. and abroad who have coordinated their publications and pooled their data for analysis.

Because the course of MS is unpredictable, clinical trials are challenging. Researchers are hopeful that the interleukin-7 receptor will provide sufficient motivation to endure the expense of long clinical trials.

With these findings, researchers may be able to perform blood tests to identify people with the flawed genes and begin to develop drugs to counteract its effects.

One drug on the market, daclizumab (Zenapax), already works on interleukin-2 and is currently in a Phase II clinical trial exploring its potential use alone and in combination with other immune-modulating drugs in MS.

Unraveling the genetic mystery of MS is proving harder than other autoimmune diseases caused by one or two malfunctioning genes. MS appears to involve defects in many genes, each with only a modest effect. The newly identified defects, by themselves, raise the risk of MS by about 20 percent. The studies also found evidence that a dozen other genes may be linked to MS, providing future potential targets for MS researchers.

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ETHNICITY IN MS
According to a recent study in Neurology, differences in immune systems have been found in African Americans with MS compared to Caucasians.  These differences could begin to explain why African Americans experience more disability with MS than Caucasians.

The study compared levels of antibodies in the cerebrospinal fluid of 66 African Americans to 132 Caucasians with MS. Antibody levels in the cerebrospinal fluid of African Americans with MS were 29 percent higher than levels found in Caucasians.

According to John R. Rinker, MD, with the Washington University School of Medicine in St. Louis, "The findings show that ethnic differences in MS extend to the immune response system, which plays a central role."  He also noted that recent genetic studies in MS have begun to identify certain genes which may explain why African Americans experience more disability, but the products of these genes and the mechanism of their effects remain unknown.

Researchers also noted that African Americans who had MS may need a cane, walker or wheelchair at an average of nine years compared to an average of 17 years for Caucasians.

"It has always been noted that, on average, African Americans seem to follow a more aggressive course with MS. For example, the Optic Neuritis Treatment Trial showed poorer recovery of visual function in African Americans than Caucasians," explains Ben Thrower, M.D. "The possible silver lining is that African Americans are generally diagnosed more quickly, perhaps due to presenting with more 'typical' symptoms. This could lead to earlier intervention."

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RESPONSE TO INTERFERON BETA PREDICTED BY MRI

According to a study presented at the 17th meeting of the European Neurological Society, magnetic resonance imaging (MRI) of brain lesions at the beginning of treatment and after one year of treatment with Interferon beta (IFN-b) can help identify individuals with MS who do not respond to IFN-b treatment.

"Early identification of nonresponders may help neurologists in their decision about MS treatment," said Carlo Pozzilli, MD, Multiple Sclerosis Centre, S. Andrea Hospital, Rome, Italy. Dr. Pozzilli is head of the research team that performed the retrospective study involving 345 patients (101 men and 244 women) who had been treated with IFN-b for an average of 4.5 years. At the beginning of the study, subjects had a mean disease duration of 5.5±4.9 years and a median Expanded Disability Status Scale (EDSS) score of 1.5 (range 0-4.5).

The researchers analyzed EDSS scores and MRI scans at baseline and after one year of IFN-b treatment of all individuals who completed the study. For subjects who discontinued IFN-b therapy, the final EDSS score was calculated at the last neurological assessment during IFN-b treatment.

Those with an increase of at least 1 point on the EDSS score (confirmed in two consecutive visits separated by a 6-month interval) were considered to have a "poor clinical response." Disease activity was determined based on the presence of gandolinium-enhancing (Gd-enhancing) lesions in post-contrast T1-weighted scans and on the accumulation of hyperintense lesions on T2-weighted images.

Individuals who had longer disease duration at the beginning of treatment and a higher baseline EDSS were more likely to have a poor response to IFN-b therapy. A relapse within the first year of IFN-b therapy also was associated with an increased likelihood of poor response over the study period.

However, investigators found that MRI data were even stronger predictors of long-term outcome, whereby both the presence of at least one Gd-enhancing lesion at 1-year and an increase in T2 lesion burden were related to a poor outcome.

"This emphasizes the importance of MRI monitoring, which not all doctors believe in," comments MSF Medical Advisor, Ben Thrower, M.D. "Beta interferon should prevent new T2 and enhancing lesions. When it does not, it probably means that the drug is not right for that person, the dose is not high enough, or there is a lack of compliance to therapy."

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MSF NEWS

IT'S BRIGHTER TOMORROW GRANT TIME AGAIN
Each year, the MSF makes dreams come true for individuals with MS through the Brighter Tomorrow Grant Program. The goal of this national program is to provide goods or services to those with MS to improve quality of life by enhancing safety, self-sufficiency, comfort, or well-being. Applications are confidential and will be reviewed by the grant committee. The Brighter Tomorrow Grant is a wish-based program and is not based solely on financial need.

Applicants are asked to provide basic personal and financial information, along with a brief essay of 100 words or less, to describe their need and how the grant might help them to have a brighter tomorrow. Applications are accepted from July 1st until October 1st. In order to be considered by the grant committee, applications must be received during these dates only.

Applications are now available on our website. Visit http://www.msfocus.org/programs_grants_bwmg_app.php. Applications will also arrive in the summer issue of MSFocus. Additional applications can be obtained by calling 1-888-MSFOCUS (673-6287). Previous grant recipients are ineligible

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SIXTH ANNUAL CAREGIVERS' NIGHT OUT CONTEST
Has someone in your life gone above and beyond the call of duty to help you?  Then, honor them this November during National Family Caregivers Month! Whether this special someone is a friend, relative, child, or significant other, we want to hear how they have made a difference in your life. Handwriting and writing style are unimportant. We're seeking stories with heart! Winners will receive dinner for two at a restaurant of their choice and their story and photo will be published in the winter issue of MSFocus.

In 100 words or less, tell us what makes your caregiver special and how he or she has made a difference in your life. Be sure to include your name, address, phone number and email address.

Submissions will be accepted from July 15th through September 1st.

Application can be emailed to homecare@msfocus.org or mailed to Caregivers' Night Out Contest, Multiple Sclerosis Foundation, 6350 N. Andrews Ave., Ft. Lauderdale, FL 33309.