Multiple sclerosis (MS) – previously also known as disseminated sclerosis – is an inflammatory disease which mainly affects young adults, in which the myelin sheaths which insulate nerve fibres in the brain and spinal cord are damaged. This disrupts the communication between different parts of the nervous system, resulting in a range of signs and symptoms, including impaired motor control and balance, visual disturbances, impaired sensation and bladder function, and cognitive problems. MS is an autoimmune disorder where the body’s own immune system attacks and destroys the myelin sheaths of nerve fibres, a process termed demyelination. Although nerves have the capacity to regain their myelin sheaths (‘remyelination’), in MS this process fails to keep pace with the ongoing demyelination.
MS is the most common cause of non-traumatic neurological disability in young adults, resulting in a significant personal cost and an enormous burden on the health system, estimated at over $1.7 billion annually in Australia in 2017. Over half of affected individuals will die either directly or indirectly as a consequence of their MS.
MS may affect individuals in different ways, with new symptoms occurring in isolated attacks (‘relapsing-remitting MS’), or building up over time (‘primary progressive MS’). Between attacks, symptoms may recover completely; however, permanent neurological problems often occur, especially as the disease advances, and it may then enter a ‘secondary-progressive’ phase. The types of symptoms, their severity, and the course of the disease vary widely, reflecting the numbers and location of demyelinating plaques in the nervous system, and the frequency of relapses.
The precise cause of MS is not known, but the prevailing consensus is that the disease begins with an environmental trigger such as a viral infection, in individuals who have a genetic susceptibility, resulting in an autoimmune process which is confined to the central nervous system (CNS). The CNS is a privileged immune site, which is protected from the systemic immune system by what is known as the ‘blood-brain barrier’. Because of this, studies have not been able to fully characterize the inflammatory and immune process within the CNS in MS. Understanding more fully how the immune-mediated damage in the CNS occurs is the key to understanding MS and to developing new treatments.
Since the introduction of β-interferon in the 1990s, a number of other disease-modifying immune therapies have become available for the treatment of MS, including natalizumab (Tysabri), ocrelizumab, daclizumab, cladribine, fingolimod, dimethyl fumarate and teriflunomide. Although not a cure for MS, these treatments can reduce the number of relapses and may slow down the development of permanent damage to the CNS.
It is self-evident that identification of the disease specific target antigens will provide unparalleled and novel insights into the autoimmune process of MS, and will facilitate the development of new more effective and safer treatment strategies than are currently available, and could ultimately also lead to strategies for prevention of the disease.