I am truly excited by the recent research into the metabolic processes behind MS…
Research conducted in the past 3 years is looking to the Kv1.3 a voltage gated channel. This channel is encoded by the KCNA3 gene in humans and is responsible for a myriad of functions. In particular disease-associated myelin-specific T cells from the blood are predominantly co-stimulation-independent effector-memory T cells that express high numbers of Kv1.3 channels. T cells in MS lesions in postmortem brain lesions are also predominantly effector-memory T cells that express high levels of the Kv1.3 channel. In children with type-1 diabetes mellitus, the disease-associated insulin- and GAD65-specific T cells isolated from the blood are effector-memory T cells that express high numbers of Kv1.3 channels, and the same is true of T cells from the synovial joint fluid of patients with rheumatoid arthritis. T cells with other antigen specificities in these patients were naive or central memory T cells that up-regulate the KCa3.1 channel upon activation. Consequently, it should be possible to selectively suppress effector-memory T cells with a Kv1.3-specific blocker and thereby ameliorate many autoimmune diseases without compromising the protective immune response. In proof-of-concept studies, Kv1.3 blockers have prevented and treated disease in rat models of multiple sclerosis, type-1 diabetes mellitus, rheumatoid arthritis, contact dermatitis, and delayed-type hypersensitivity. http://www.ncbi.nlm.nih.gov/pubmed/19538097
Metabolic Kv1.3 is also considered a therapeutic target for the treatment of obesity, for enhancing peripheral insulin sensitivity in patients with type-2 diabetes mellitus, and for preventing bone resorption in periodontal disease. A genetic variation in the Kv1.3 promoter region is associated with low insulin sensitivity and impaired glucose tolerance. This addresses many of the potential links to gut microbes and the insulin/glucose issue in MS.
obesity and insulinhttp://www.ncbi.nlm.nih.gov/pubmed/23729813
The truly incredible news is a drug has already been created 124 years ago… yes, in 1890, that targets Kv1.3. Clofazimine, a drug originally manufactured in 1890 to prevent leprosy is being considered for MS. The reason is it targets the Kv1.3 channel. It lacks any serious side effect aside from potential gastro-intestinal issues but it lacks potency and must be optimized for use against auto-immune diseases. This drug is regularly available cheap in developing countries but Canada, US and most other nations will not permit people to take it. Interestingly, the Kv1.3 blocker clofazimine has been reported to be effective in the treatment of chronic graft-versus-host disease, cutaneous lupus, and pustular psoriasis in humans. Furthermore, clofazimine in combination with the antibiotics clarithromycin and rifabutin induced remission for about 2 years in patients with Crohn's disease, but the effect was temporary; the effect was thought to be due to anti-mycobacterial activity, but could well have been an immunomodulatory effect by clofazimine.
Clofaziminehttp://www.ncbi.nlm.nih.gov/pubmed/?ter ... ymphocytes
Story from my neck of the woods…http://www.cbc.ca/news/canada/british-c ... -1.1413465
Aside from Clofazimine Kv1.3 is blocked by several peptides from venomous creatures including scorpions, margatoxin, kaliotoxin, charybdotoxin, noxiustoxin, anuroctoxin, and sea anemone (ShK-F6CA, ShK-186, ShK-192, BgK), and by small molecule compounds (e.g., PAP-1, correolide, benzamides,CP339818, and progesterone.) Progesterone being very interesting as many have sited this hormone as being effective in MS treatment. At therapeutic concentrations, the blockers did not cause any clinically evident toxicity in rodents, and it did not compromise the protective immune response to acute influenza viral infection and acute chlamydia bacterial infection.
Its important to note that it will likely be 10 years before a drug is released that treats MS in this way as Big Pharma has to make a more potent form of Kv1.3 then has to figure out how to make money off of it... One of the major studies on the drug is being done in Hawaii. Two researchers on the big island were the first to think of using the drug for MS, and quickly put a patent on the idea... kind of ridiculous that a patent can be put on the idea of using a 124 year old drug for a new purpose. A study on Kv1.3 blockers is also being conducted in Seattle.