遺伝症候群と遺伝子治療のジャーナル
オープンアクセス

概要

Stem Cell-based Therapies in Multiple Sclerosis

Kimiskidis VK and Fassas A

The method of intensive immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HSCT) has been used in the last eighteen years for the management of severe forms of Multiple Sclerosis (MS) and has been claimed to yield superior results. However, it is still not an established method of MS treatment, because it has not demonstrated its superior efficacy in comparative trials, owing to methodological difficulties and lack of sufficient patient recruitment. The main criticism has been the transplant-associated toxicity and an approximately 3% risk of mortality. Based on the results of these studies, HSCT has a sustained effect in suppressing disease progression for long periods of time, while it may also bring about sustained clinical improvement, especially if patients are in the relapsing-remitting phase or have active Magnetic Resonance Imaging (MRI) lesions. Three particular points merit to be stressed: (a) the nearly 100% eradication of active Central Nervous System (CNS) lesions on MRI, sustained over time; (b) the dramatic effect on the so-called “malignant” MS forms; (c) the qualitative immunological changes post-HSCT resulting in reconstitution of the clonal diversity and in regeneration of regulatory cells. Whether the latter changes, can also result in immune tolerance is yet to be definitely shown. An alternative approach to HSCT involves the transplantation of Mesenchymal stem cells (MSCs). This interesting approach has been explored in a limited number of phase I/II studies with promising results that await confirmation in the context of larger scale, controlled trials. In conclusion, HSCT is not a therapy for the general population of MS patients; it is a powerful therapy with long-term benefits that need to be weighed against certain toxicity risks; and in critical situations, like the very aggressive, rapidly progressing and refractory “malignant” form, it may have a life-saving effect with a meaningful and long-lasting improvement of disability.