Stem cell and gene therapeutic strategies for the treatment of multiple sclerosis

Abstract

Multiple sclerosis is a disease of the central nervous system that predmoninantly affects young adults. The pathogenic mechanisms are complex, however numerous studies indicate that the disease is initiated by an autoimmune attack on protein targets present in the central nervous system. Given that a dysfunctional immune system perpetuates the pathophysiological mechanisms that characterize this inflammatory disorder, several therapeutic approaches that target immune cells or their secreted mediators have been generated and are currently used clinically. Although these strategies have been partially beneficial to a proportion of patients, current therapies are not particularly effective at preventing disease progression. As such there is a large and unmet need for the development of more effective treatments. Owing to a number of promising results obtained in mouse models of multiple sclerosis, cell therapies implementing hematopoietic, mesenchymal and neural stem cells may provide practical vehicles for in situ immunomodulation, neuroprotection and regeneration. In concert with these approaches, gene therapy strategies are being investigated to restore antigen-specific tolerance or to deliver anti-inflammatory molecules. Furthermore targeted delivery of glial or neurotropic factors, which counteract the activity of inhibitory molecules within the neurodegenerative component of the lesion, is also being pursued. It is conceivable that these experimental approaches alone, or in combination with emerging and current treatments, may establish a rational protocol for the treatment of multiple sclerosis and potentially other autoimmune disorders.