Pharmacotherapy Options for Multiple Sclerosis: Focus on Natalizumab

Multiple sclerosis (MS) is considered an autoimmune disease causing demyelination in the central nervous system (CNS) that subsequently leads to axonal damage and neurological impairment. Currently available first line therapies are based on immunomodulation with beta-interferons or glatirameracetate. However, these treatments are only partially effective, thus, more powerful therapies represent an unmet need in MS. Natalizumab is a monoclonal antibody targeting the alpha 4 beta 1 integrin that has been shown to be crucial in the process of transmigration of immunocompetent cells across the blood-brain-barrier (BBB) into the CNS. Two phase III trials have demonstrated clinical and paraclinical efficacy of natalizumab and recent data suggest that many patients that have failed on a first-line disease modifying drug (DMD) benefit from a treatment with natalizumab. Unfortunately, since the licensing of natalizumab in 2006 there have been 75 cases of progressive multifocal leukoencephalopathy (PML) reported. This rare, but potentially fatal infection of the brain by JC-virus restricts the use of natalizumab. Currently there are attempts to define algorithms based on the identification of risk factors for the development of PML to achieve a better safety management for MS patients treated with this monoclonal antibody.