A 21 POINT UNIFYING HYPOTHESIS ON THE ETIOLOGY AND TREATMENT OF MULTIPLE-SCLEROSIS

Multiple sclerosis (MS) is postulated to be a cell mediated autoimmune disease directed against central nervous system myelin components. Ou r understanding of the disease has been enhanced by a number of factor s: 1) advances in our understanding of the immune system; 2) clinical trials which are beginning to identify treatments which can affect MS; 3) a better understanding of the clinical features of MS; and 4) adva nces in MRI imaging of the brain. Based on the current state of knowle dge, this paper proposes a 21 point unifying hypothesis on the etiolog y and treatment of the disease. This hypothesis makes a series of assu mptions, many of which are unproven, and is presented as a framework f rom which to investigate and treat the disease, not as a established b iology. It is hypothesized that the underlying pathogenesis of MS is r elated to an inappropriate class of immune response against myelin ant igens favoring proinflammatory Th1 versus anti-inflammatory Th2 or Th3 type responses. Environmental and genetic factors predispose toward M S by affecting the class of response and effectiveness of treatment is also related to how it impacts on this common final pathway. Because of epitope spreading, there is not one autoantigen involved in MS and the progressive form of MS differs immunologically from the relapsing remitting form. Viruses trigger and perpetuate MS, although MS is not related to a persistent viral infection. Because MS is a multifactoria l disease, there are clinical and perhaps immunological subtypes of MS and a single type of treatment is unlikely to control the disease in all patients. Thus, there will be responders and non-responders to eac h effective therapy and ultimately combination therapy will be require d to cure the disease.