Multiple sclerosis (MS) is an inflammatory disease of the CNS characterized by myelin loss, varying degrees of axonal pathology, and progressive neurological dysfunction; the symptoms vary widely and may affect vision, hearing, cognition, balance, and movement. To date there is no cure for MS, and although treatments that modestly impact on new disease activity exist, they present several serious or even life-threatening adverse effects, including liver damage, cardiac disease, Grave’s disease, leukemia and progressive multifocal leukoencephalopathy.
MS is one of the most prevalent diseases of the central nervous system (CNS), affecting over two million people worldwide. North America has one of the highest rates of MS in the world with an estimated 400,000 Americans and 75,000 Canadians living with this disease. The annual cost of medical care has been estimated between $30,836 and $77,981 per patient depending on the severity of disease, even before considering the non-economic impact to an individual’s quality of life. This economic and personal burden makes unraveling the etiology of MS and the development of knowledge-based treatments a high priority.
Pathogenesis & Clinical Features
Attacks of MS vary in episodes and can occur months or years apart between episodes. Numbness in the hand that could resolve can be followed up months later with weakness in the legs. Full recoveries from MS attacks vary between individual patients. The presentations of clinical features include sensory loss, cognitive impairment, ataxia, depression/bipolar disorder, optic neuritis, irregular twitching of facial muscles and visual hallucinations. Fatigue is the most common in MS, 50-60% of patients develop fatigue followed by cognitive dysfunction ranges from 40-60% in MS patients. Pain is also a common occurrence with 30-50% of patients, primary pain is due to the demyelination event on its own and secondary pain is from spasticity. A small portion of MS patients may also experience seizures, aphasia or dysphasia.
Current Therapies/Future Aims
Most drugs for the treatment of MS are for relapsing-remitting multiple sclerosis: this includes interferon beta-1a, interferon beta-1b, glatiramer acetate, mitoxantrone, natalizumab, fingolimod, teriflunomide, and dimethyl fumarate. Interferon beta balances the pro and anti-inflammatory agents in the brain. It reduces the numbers of inflammatory cells that cross the blood brain barrier. Glatiramer acetate is similar to myelin basic protein and competes for presentation to T cells. Studies on interferon-beta-1b do not support that it slows progression but does reduce the number of relapses.
MS was originally considered an autoimmune disease triggered by exposure to environmental agents, such as viral infections and smoking habits. However, family and twin studies have clearly demonstrated that, like many other common neurological conditions, MS aggregates in families, highlighting a strong genetic component to disease that interacts with environmental factors. The index of heritability found in these studies varies widely from 0.25 to 0.76, reflecting differences in sample sizes between studies and patient recruitment, disease definition, and population studied; however, the overall conclusion is that genetic factors are important in the pathogenesis of this disease. Some of the genetic components implicated in the biology of MS have already been identified through genome-wide association studies (GWAS). Although these studies have conclusively proven that common genetic variants in genes, primarily related to the immune system, are associated with disease risk, functional variants responsible for the onset of disease have remained elusive.