Intraspinal stem cell transplantation for amyotrophic lateral sclerosis.

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder in which the loss of upper and lower motor neurons produces progressive weakness and eventually death. In the decades since the approval of riluzole, the only US Food and Drug Administration-approved medication to moderately slow progression of ALS, no new therapeutics have arisen to alter the course of the disease. This is partly due to our incomplete understanding of the complex pathogenesis of motor neuron degeneration. Stem cells have emerged as an attractive option in treating ALS, because they come armed with equally complex cellular machinery and may modulate the local microenvironment in many ways to rescue diseased motor neurons. Various stem cell types are being evaluated in preclinical and early clinical applications; here, we review the preclinical strategies and advances supporting the recent clinical translation of neural progenitor cell therapy for ALS. Specifically, we focus on the use of spinal cord neural progenitor cells and the pipeline starting from preclinical studies to the designs of phase I and IIa clinical trials involving direct intraspinal transplantation in humans.