Multiple Sclerosis

Multiple sclerosis (MS) is thought to be an autoimmune disease in which the bodys immune system attacks the cells of the brain. MS is a neurodegenerative autoimmune disease that affects approximately 350,000-500,000 people in North America alone and the incidence is higher in women than men. The precise cause of MS is not known however, it is considered to be associated with the infection of viruses. The disease often begins in young adults with inflammatory attacks against the nerve, mainly the insulating myelin sheaths of the brain.

Symptoms

Most people experience their first symptoms of MS between the ages of 20 and 40; the initial symptom of MS is often blurred or double vision, red-green color distortion, or even blindness in one eye.They also exhibit other signs of neuron-muscular disorders like, loss of sensation (prickling, or "pins and needles" sensations), lack of coordination, difficulty in walking and paralysis. Speech impediments, tremors, and dizziness, bowel and bladder incontinence, are other frequent complaints . Fifty percent of the MS patients experience cognitive impairments such as difficulties with concentration, attention, memory, and poor judgment.

Treatment

Thus far, there is no cure for MS. However, the FDA approved three forms of beta interferon (Avonex, Betaseron, and Rebif), a synthetic form of myelin basic protein, called copolymer I (Copaxone), and an immunosuppressant treatment, Novantrone (mitoxantrone), are clinically used to treat relapsing and remitting MS and advanced or chronic MS. FDA has also reapproved one monoclonal antibody, natalizumab (Tysabri) for the treatment. The immunosuppressive drugs such as imuran, cyclophosphamide, methotrexate and cladribine are also used , however due to dose-related bone marrow toxicity, they render patients at risk from infection and haemorrhage. Physical therapy and exercise together with muscle relaxants and tranquilizers can help preserve muscular functions.

Murine models of the disease

The biochemical constituents described as immunodominant antigenic epitopes responsible for the disease have been identified and they include myelin basic protein (MBP), proteolipid protein (PLP), myelin associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (MOG). Experimental autoimmune encephalomyelitis (EAE), an animal model of MS is induced by administration of the antigens MBP, PLP and MOG into rodents. Depending upon the use of combination of type of myelin protein and strain of mice one can mimic the human disease conditions in these experimental models.

Research: An inflammatory response consisting of primarily of CD4+ T cells and also other cells such as CD8+ and gamma deltaTCR+ T cells, plasma cells and macrophages has been observed in the lesions in the brain of mice immunized with myelin specific antigens.

Their infiltration and transmigration is influenced by the expression of chemokine and their receptors, adhesion receptor and their ligands, as well as the matrix metalloproteinases on the inflammatory cells and endothelial cells. The activated T cells play a major role in the breakdown of the blood-brain barrier and demyelination of the neurons. A role for genetic and environmental factors has also been suggested for the development of MS.

The experimental approaches for the treatment of MS include approaches that will allow skewing the cytokine profile of myelin-specific Th cells from Th1 to Th2. These have included use of altered peptide ligands (APLs), hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins"), and DNA vaccination combined with gene delivery of interleukin 4 (IL-4). APLs are peptides modified at crucial receptor binding residues so that they modulate proliferation and cytokine profile of antigen-specific T cells by altering the strength of T cell receptor (TCR) signaling. With the knowledge that MS patients go into remission during pregnancy, administration of estrogens that inhibit inflammatory response have also been considered in the treatment of MS.

CAM therapy against MS

In addition to positive attitude, exercise and well balanced diet, massage, acupuncture, use of linoleic acid present in sunflower seeds and safflower oil, use of turmeric found in Asian cuisine and Padma-28 found in health food stores and use of cannabis-based drug Sativex have been tried as CAM therapeutic agents against MS.

Study at the NIH CAM Center:

Our studies are aimed at addressing the mechanism underlying use of CAM therapy in the treatment of MS. We are testing the potential of grape derived chemical, resveratrol in the treatment of MS using murine EAE models. We will be testing the central hypothesis that resveratrol treatment is effective against EAE through multiple pathways that include induction of apoptosis in myelin-specific T cells, suppression of DC functions, decreased T cell infiltration in the CNS due to down-regulation of homing receptors such as CD44 and upregulation of T regs.

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