Setback in trials of MS therapy
Two studies presented in the October issue of Nature Medicine (Vol. 6, No. 10) report the failure of a potentially new therapy for multiple sclerosis (MS) in clinical trials. However, scientists are keen to stress that the results of these trials will benefit treatment of diseases such as MS in the long term because they provide new insights into the pathology of the disease.
Although the cause of MS is unknown, it is thought that the body’s immune system is wongly targeted to destroy a section of its own protein on the myelin sheath that covers neurons in the central nervous system. The immune cells involved in the inflammatory reaction that destroy the myelin sheath have been identified as type 1 T helper cells (Th1) which cause infllamation.
In order to trick the immune system into producing beneficial, antiinflammatory, Th2 cells rather than damaging Th1 cells, both teams of researchers constructed a compound known as an altered peptide ligand (APL), which is based on a protein segment of the myelin sheath. Depending on how this compound binds to receptors on T helper cells, different types of T cell are produced.
In both of the Phase II clinical trials, an APL compound was administered to MS patients by injection. In one study, carried out by Roland Martin’s team at the US National Institutes of Health, the trial had to be halted because the APL was poorly tolerated by patients. Treatment actually exacerbated MS by stimulating Th2 rather than Th1 cell production. A separate study lead by Lawrence Steinman at Stanford University School of Medicine was also suspended because of hypersensitivity reactions in 9% of the patients. In contrast to Martin’s study, this trial did show that APL generated the desired Th2 response.
Genain and Zamvill discuss the complexity of the biological effects of APLs and suggest that a redesign of the APLs tested may generate a compound that produces only antiinflammatory Th1 cells. They write, "The observations made by these groups should stimulate further research into which patients are most likely to benefit from APL therapy."
Dr. Roland Martin
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Building 10, Room 5B-16
10 Center DR MSC 1400
Bethesda, MD 20892-1400
Tel: +1 301 402-4488
Dr. Lawrence Steinman
Department of Neurology/Neuroscience
Beckman Center B002
Stanford University School of Medicine
Stanford CA 94305.
Tel: +1 650 725 6401
Fax: +1 650 725 0627
Dr. Claude P. Genain
Department of Neurology,
513 Parnassus Avenue
University of California,
San Francisco, CA
Tel: +1 415 502 5684
Fax: +1 415 502 5899
(C) Nature Medicine press release.
Message posted by: Trevor M. D'Souza