Promising New Therapy For MS Patients

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Main Category: Multiple Sclerosis
Also Included In: Immune System / Vaccines;  Clinical Trials / Drug Trials;  Neurology / Neuroscience
Article Date: 11 Jun 2008 - 0:00 PDT

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An article posted early online from the Archive of Neurology reports on a promising new treatment for people with multiple sclerosis (MS). Researchers have found that high doses of the drug cyclophosphamide, an immunosuppressant, have reduced MS activity and disability in people with an aggressive form of the disease.

Multiple sclerosis (MS) is an autoimmune condition in which the immune system attacks the central nervous system, leading to the degeneration of the coating that protects nerve cells (called the myelin sheath). The inflammatory disease impairs physical and cognitive function by impeding the nervous system's ability to send electrical signals. Each of the four identified MS subtypes has a distinct autoimmune process, and this has made it difficult to find optimal therapies that can intervene with the immune system to treat MS.

With mixed results, the drug cyclophosphamide has been used to treat MS because it affects the functions of the immune system's T and B cells. The therapy is usually combined with bone marrow transplantation. To further investigate how high doses of the drug (without bone marrow transplantation) affect patients with aggressive relapsing-remitting MS, Chitra Krishnan, M.H.S. (Bloomberg School of Public Health, Johns Hopkins University, Baltimore) and colleagues conducted a two-year open-label trial with six men and three women who averaged 35 years of age. In relapsing-remitting MS (the most common form), patients experience both periods of symptoms and periods of symptom-free remission. The treatment consisted of 50 milligrams per kilogram per day of cyclophosphamide, injected intravenously for four consecutive days.

During the 23 months (average) of follow-up, none of the patients died or had unexpected or serious adverse events. The researchers found that on tests measuring physical and mental function, the patients recorded an 87% improvement. They also saw a 39.4% decrease in disability. Measuring the average number of MS-related brain lesions using magnetic resonance imaging (MRI), the researchers found a significant decrease from 6.5 to 1.2 lesions.

"High-dose cyclophosphamide treatment of patients with aggressive MS was safe and well tolerated and did not lead to excess morbidity or accelerated brain atrophy," highlight the authors. "Moreover, high-dose cyclophosphamide induced a functional improvement in most of the patients we studied. In many of those patients, the functional improvement was sustained through the length of the study (up to 24 months) despite the absence of any immunomodulatory therapies beyond the initial high-dose cyclophosphamide treatment."

They conclude that, "This immunoablative regimen [an immune-related therapy involving the destruction of a cell population] of cyclophosphamide for patients with aggressive MS is worthy of further study and may be an alternative to bone marrow transplantation."

Reduction of Disease Activity and Disability With High-Dose Cyclophosphamide in Patients With Aggressive Multiple Sclerosis
Chitra Krishnan, MHS; Adam I. Kaplin, MD, PhD; Robert A. Brodsky, MD; Daniel B. Drachman, MD; Richard J. Jones, MD; Dzung L. Pham, PhD; Nancy D. Richert, MD, PhD; Carlos A. Pardo, MD; David M. Yousem, MD, MBA; Edward Hammond, MD, MPH; Megan Quigg, BA; Carrilin Trecker, BA; Justin C. McArthur, MBBS, MPH; Avindra Nath, MD; Benjamin M. Greenberg, MD, MHS; Peter A. Calabresi, MD; Douglas A. Kerr, MD, PhD
Archives of Neurology (2008). 65[8].
doi:10.1001/archneurol.65.8.noc80042
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Written by: Peter M Crosta
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