Cholesterol-lowering drugs could treat multiple sclerosis

May 13 2004

Drug treatments for MS are expensive and only partially effective. Recent knowledge that statins promote an anti-inflammatory response from the immune system suggest a potential in the treatment of MS.

Inderjit Singh from the Medical University of South Carolina, USA, and colleagues report how 30 people with MS given 80 mg simvastatin daily for 6 months had a 44% reduction in the proportion of brain lesions after three months of treatment compared with lesions identified before treatment initiation.

Dr Singh comments: "These findings suggest that an 80 mg daily dose of oral simvastatin over a 6 month period could inhibit the inflammatory components of multiple sclerosis that lead to neurological disability...Our results, combined with the published work on the immunological effects of statins lend support to the case for randomised controlled clinical trials to establish the safety and efficacy of statins in the treatment of relapsing-remitting multiple sclerosis".

In an accompanying Commentary (p 1570), Chris Polman from VU Medical Centre, Amsterdam, Netherlands, concludes: "...[this] study is a big step forward because it is the first to provide some evidence of an effect with a statin in multiple sclerosis-but it is only an initial step. Additional data are required to more precisely determine the clinical effects of statins, to explore the optimum dose, the therapeutic window, and the differential potency of statins, and to evaluate whether combination therapy might be more effective than monotherapy. Physicians, scientists, drug companies, and regulatory agencies should now work together to design and do randomised studies that have adequate power to address these and other important issues. It is the joint responsibility of all involved to ensure that some of the potential charms of statins (low-hurdle access, convenience, low cost) do not develop into a dangerous boomerang, in case proper studies become jeopardised by widespread off-label use".

The potential for statins as treatment for MS is also discussed in a review in the June issue of THE LANCET NEUROLOGY (page 369-71). Author Hans-Peter Hartung comments: "The obvious advantage of statins over existing MS therapies is their oral route of dosing. Statins might be beneficial for MS patients as monotherapy or as an add-on to established disease modifying drugs. As the evidence of the benefit of statins in MS is currently insufficient, large controlled clinical trials are needed. The first of these trials is about to start".

Multiple sclerosis (MS) is a non-contagious chronic autoimmune disorder of the central nervous system which can present with a variety of neurological symptoms occurring in attacks or slowly progressing over time.

The ultimate cause of MS is unknown. It is hypothesised that a viral infection or other environmental factor in childhood might prime the immune system for an abnormal reaction later in life. On a molecular level, there might be a structural similarity between an unidentified infectious agent and components of the central nervous system, causing confusion in the immune system later in life (a process called "molecular mimicry"). However, so far there is no known "MS virus". Certainly MS is not an infectious disease and not contagious. The importance of genetic factors has been discussed above.
 
It is widely accepted that a special subset of white blood cells, called T cells, play a key role in the development of MS. Under normal circumstances, these lymphocytes can distinguish between self and non-self. In a person with MS, however, these cells recognize healthy parts of the central nervous system as foreign, and attack them as they would a virus. In MS, the part of the nervous system primarily attacked is myelin. Myelin is a fatty substance that covers the axons of nerve cells, and which is important for proper nerve conduction. Normally, there is a tight barrier between blood and brain, called the blood-brain barrier (BBB), built up of endothelial cells lining the blood vessel walls.

In MS, the BBB breaks down; autoreactive T cells cross the BBB and trigger an inflammatory process, also mediated by other immune cells, such as cytokines and antibodies. Due to this abnormal behavior of the immune system, MS is considered to be an autoimmune disorder. The inflammatory process finally leads to a destruction of myelin called demyelination. Repair processes, called remyelination, also play an important role. This is one of the reasons why, especially in early phases of the disease, symptoms tend to decrease or disappear temporarily after days to months. Nevertheless, axonal damage and irreversible loss of neurons occur early during the course of the disease. However, due to its plasticity the brain can often compensate for some portion of the damage. MS symptoms develop as a result of multiple lesions in the brain and spinal cord, and can vary greatly between different individuals, depending on where the lesions occur.

http://en.wikipedia.org
Some text is available under the terms of the GNU Free Documentation License
http://en.wikipedia.org/wiki/Wikipedia:Text_of_the_GNU_Free_Documentation_License