Is there a cure for MS in the nearI

future? I

The old aphorism "nothing is impossible, but some things are just more difficult" is an appropriate response to this challenge. A cure for MS is not likely. Just as men and women recover from heart attacks and lead productive lives, patients can function well with a diagnosis of MS.

Although a half century ago rational treatment of MS seemed improbable, if not impossible, treatments proven to reduce the risk of attacks and disability have become a reality in the last 12 years. Consequently, we all eagerly await new developments in the field of MS treatment. Better experimental treatment designs and more effective drugs are anticipated. If a drug is to be used, it first must be shown to be safe. Then, and only then, is it permissible to investigate the effectiveness of the new drug in patients.

A report of the preliminary efficacy studies of natal-izumab (Tysabri) appeared in the New England Journal ofMedicine 2 years ago. The pivotal study, reported at the annual American Academy of Neurology meeting in Miami Beach in April 2005, provided evidence that this new drug was even more effective than it had appeared to be earlier and provided the basis for FDA approval. Despite the excitement regarding its earlier appearance of safety and efficacy, it has now been withdrawn from the market for safety reasons. When combined with Avonex, it appears to be excessively immunosuppressive and resulted in PML in two cases. This new drug with its unique mechanism of action may be too effective to allow combination therapy, at least with interferons. The facts of the matter will have to be elucidated to determine whether it can be rein-troduced for the treatment of MS.

Karen's comment:

One of my nieces was in an advanced science program at the age of 7 years. The class assignment was to invent something new; hers was to fix "Multiple Skleroys." Although her spelling was not accurate, her sentiment is one shared by many. When I was first diagnosed in 1996, the pundits predicted a cure for MS in 5 years. Five years later the anticipated cure was within 10 years. Now it is said, '"Perhaps within my lifetime."

Over the years, my thinking about cure has also evolved—not just about an ever-extending time line but also the meaning of cure. As a retired lawyer and non-retired bibliophile, the definition of a word is important to me. "Cure"—does it mean all people who get MS after a cure is found will be made disease-free; all people who have MS now will become disease-free or symptom-free; existing MS brain and nerve damage will be repaired; or no one will get MS?

Until a cure is found, whatever it means, I view my role as threefold: to give my support, financial and other, to those people and organizations working on a cure; to volunteer my body, alive and dead, to researchers working on a cure; and to keep myself physically, mentally, and spiritually as strong as possible to be ready for a cure and to be ready if a cure is not found in my lifetime. I have confidence in my niece.

99. What is the future? I

Advances in the therapy of MS and autoimmune dis- I

ease in general will certainly continue just as they have I

in other disorders. Although T-cell vaccination has some promise, results to date have been somewhat disappointing, but those trials are continuing. A dream treatment of eliminating immune reactions aimed at myelin, a theoretical possibility, when given early in the course of disease could result in permanent cessation of clinical activity. This third-generation type of T-cell vaccine would induce permanent immune tolerance to an offending antigen (protein) and could be a "one-shot cure." There are no current trials in progress, but this approach will certainly be revisited.

With the improved understanding of disease mechanisms and the dangers and limitation of selective adhesion molecule modulation, it is anticipated that in the future oral drugs may replace the use of IV medication (Tysabri). Preliminary efficacy (Phase II) trials of a product employed by Glaxo-Smith Kline have apparently achieved results resembling those of natal-izumab. If these drugs achieve similar or equal effectiveness and are safe, they will gain rapid acceptance. Because trials have been stopped, they will not become

Immunomodulation treatment aimed at changing immune responses to benefit a patient with autoimmune disease.

a reality in the immediate future. Other approaches blocking IL-12, a hormone essential to the immune cascade, with monoclonal antibodies are currently being employed by two pharmaceutical companies. Hopefully, these studies will lead to the availability of alternative safe and effective mechanisms of immunomodulation in MS. Because of the need to compare effectiveness of treatment rather than to compare a given treatment with placebo, fewer drugs are likely to enter future trials. However, a number of newer approaches to management are entering trials now, and only time will tell if they truly represent safer and/or more effective treatments.

The surprising new findings in Crohn's disease of a new genetic mutation in 80% of a subset of patients that provides a "rational" explanation for the illness seemed unlikely just a year ago. This is now is a reality; however, no one really anticipates finding an "MS" gene. However, this new finding in Crohn's disease exemplifies now that good genetic and biological research can provide unanticipated new discoveries in medicine. Research is the key to the future in MS, as it is for all of the biological sciences and in medicine.

Karen's comment:

Unpredictable, unknowable, and uncertain are all characteristics of the future for a person with MS. As a person of reason, I think that these characteristics hold true for everyone, MSers and non-MSers alike. As a person of faith, I believe that there is also hope.

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