Progress and prospects for the use and the understanding of the mode of action of autologous hematopoietic stem cell transplantation in the treatment of multiple sclerosis.

INTRODUCTION: A substantial proportion of patients with multiple sclerosis (MS) do not respond to pharmacological treatments and no currently approved therapy has been convincingly demonstrated to prevent or stop disease progression. With MS widely believed to be an auto-immune disease, immunoablative therapy followed by autologous haematopoietic stem cell transplantation (I/AHSCT) is being investigated as an alternative therapeutic option. Areas covered: With the results of phase III comparative trials only a few years away, this article reviews animal and clinical trials of I/AHSCT in the treatment of MS and discusses possible immunological mechanisms behind its action. Expert commentary: I/AHSCT can induce long-term suppression of inflammatory disease activity and can halt or reverse neurological deterioration even in progressive stages of the disease, altering the fundamental disease course. However, toxicity of the therapy remains a problem and longer term follow up is required. Immunological investigations of the reconstituting immune system have discovered that qualitative changes take place at the cellular and molecular levels, which support the hypothesis of a 'resetting' of the immune system towards a tolerant and anti-inflammatory state.