July 11, 2003
Amit Bar-Or, M.D.
Neurologist and Neuroimmunologist, McGill University and the Montreal Neurological Institute
This is the last of a three-part Viewpoint series that provides an update on some of the new treatment approaches in the field of MS, as reported at the recent American Academy of Neurology (AAN) annual meeting. As in the first two parts of this series, we will try to understand the rationale for considering these agents as potential therapies for MS, based on their presumed mechanism of action on the biology of the illness. Readers may wish to refer to some of the earlier Viewpoints which describe a simplified model of the way the immune system is thought to cause damage to the central nervous system (CNS) of patients with MS, and how the currently approved immune modulators are thought to mediate their benefits.
While the four therapies (alphabetically: Avonex®, Betaseron®, Copaxone® and Rebif®) currently approved for the treatment of relapsing remitting MS (RRMS) have all been shown to significantly decrease the relapse rate and the accumulation of new lesions on brain MRI, these therapies remain only partially effective, require injections and have side-effect profiles that may impact on patients’ quality of life. As noted in the previous two Viewpoints of this series, the recent American Academy of Neurology (AAN) Annual Meeting was the platform for approximately 75 posters and presentations on novel treatment approaches for MS. One area of renewed focus relates to ‘naturally occurring’ or ‘dietary’ substances.
Comprehensive studies of dietary risk factors or dietary supplementation in MS are very difficult to do and to interpret. Results of studies that rely on trying to recall whether or not a given factor (such as a particular dietary exposure or lack of exposure) was present years before the diagnosis of MS may, understandably, be unreliable. Furthermore, the great majority of studies that aim to examine the potential role of such factors in MS can, at best, identify an association between a given factor and the risk of MS, but cannot prove that the factor actually causes MS, or truly participates in the process of the illness. In spite of these limitations, it is now well accepted in the MS scientific community that unknown factors in the environment are important in determining the risk of MS. The fact that MS is not evenly distributed around the globe, and occurs much more frequently in certain regions, or in certain populations, has continued to intrigue researchers. Some of the suggestions put forth to explain these observations have focused on the roles of different dietary habits and distinct climates (including exposure to sunlight). It remains attractive to think that the risk of developing MS, or how active someone’s MS is, could be affected through modification of one’s diet. In the last few years, several laboratory-based studies have been emerging that identify, from a biological perspective, how certain dietary factors indeed influence the immune system, and how they may represent viable targets for future MS therapies.
At the recent AAN Meeting, Dr. Weinstock-Guttman and colleagues (1) set out to study the effects of adding a low-fat diet supplemented with a particular type of fatty-acids known as long chain polyunsaturated fatty acids (PUFA) to standard immune modulating therapy. They chose this fatty-acid supplement because of prior laboratory evidence showing that PUFA can modulate the function of immune cells in ways that may be beneficial in autoimmune conditions such as MS (2). Patients with RRMS taking either interferon-beta or glatiramer acetate were randomly assigned to either a diet including PUFA or a standard low-fat diet, as a control. Of 32 patients enrolled, 29 were assessed with an average follow up of about 10 months. Both diets were well tolerated but compared to patients receiving the standard low-fat diet, the patients receiving PUFA supplementation were reported to have fewer attacks and possibly less worsening of disability. This work extends prior open label studies that also suggested a role for PUFA in decreasing inflammation in MS.
At a more basic level, Marracci and colleagues studied which parts of fatty acid molecules may be most important in mediating their anti-inflammatory effects (3). They used an animal model of MS, EAE, and found that manipulating the structure of the fatty acids resulted in compounds that had different abilities to suppress EAE. These results further support the potential role of using fatty acid derivatives as a therapeutic approach in MS and provide useful structural information that may enable the design of more effective derivatives.