This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system (CNS) in humans. Onset typically occurs between ages 20 and 40, thus making MS the leading cause of atraumatic neurological disability in young adults. Approximately 300,000 (0.1%) individuals in the United States have been diagnosed with MS. Inflammatory demyelinating lesions in MS can occur throughout the CNS, accounting for the variety of neurological signs and symptoms that may develop in individual patients. Frequently, MS patients present with a clinically isolated syndrome (CIS) with only one set of neurological presentation suggestive of MS. The presence of MRI lesions in patients with CIS has been highly predictive of a future diagnosis of MS. More than 85% of patients with MS initially experience a relapsing-remitting (RR) course with clinical exacerbations of neurological symptoms, followed by recovery that may or may not be complete. Although 10% to 20% of patients with MS have a 'benign' form, 50% of the patients develop a significant limitation to ambulate and require assistance after 10 to 15 years of MS evolution. Statins have been successfully used to treat cardiovascular diseases due to abnormal lipid profile. It is believed that statins exert their beneficial effects, at least partly, through an anti-inflammatory process. Multiple sclerosis is generally viewed as an inflammatory disease of the CNS caused by autoreactive antibodies against myelin. In a murine model of experimental autoimmune encephalitis (EAE), an experimental model for MS, atorvastatin has shown immunomodulatory activity that may be beneficial in MS treatment.Furthermore, simvastatin, another agent in the statin family, has shown promising effect in an open label study of the relapsing remitting form of MS (RRMS) in humans. A more recent study showed that Simvastatin treatment in patients with relapsing remitting MS was associated with a decrease the mean number of gadolinium enhancing lesions on MRI at months 4,5 and 6 of treatment compared to pre treatment MRI scans.All approved therapies for MS have profound immunological effects and employ immunomodulatory strategies. Due to a high toxicity profile and parenteral use, these agents are reserved for established disease. Avonex (interferon -1a) has been recently approved for patients presenting with CIS and magnetic resonance imaging (MRI) findings suggestive of MS. Interferon -1a requires weekly intramuscular injections and has a high toxicity profile. Due to the irreversiblity of the demyelinating process in CNS and high morbidity of MS, it is of great interest to develop early interventional measures that possess both ease of administration and a minimal toxicity profile. This study will also examine whether early intervention in patients with CIS may result in a state of immunological tolerance and whether atorvastatin has any residual effect after discontinuation. This may enable the patient to be withdrawn from therapy after a certain period of receiving treatment.
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