Neural stem cell transplantation in ALS: Developing a cure for the incurable?

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron (MN) disease and usually causes death through respiratory muscle failure within 2-5 years of symptom onset, following progressive loss of function and considerable disability. Riluzole is currently the only disease-modifying therapeutic agent, and following recent advances in stem cell technology, the feasibility of introducing cells into the central nervous system (CNS) is being investigated. Neural stem cells (NSCs) and their derivatives have the potential to replace lost MNs and, via neurotrophic factor secretion, slow progression and stimulate regeneration through endogenous repair mechanisms. Prolonged survival and functional improvement have been demonstrated in ALS mouse models transplanted with NSCs and early clinical trials have shown NSC intraspinal injections to be safe in patients. However, issues of ethics, immunosuppression, tumour risk and technique standardization need to be addressed before NSC transplantation can become part of clinical practice. It is realistic that NSCs could be used to slow disease progression, prolong survival and even effect functional improvement in ALS, but the feasibility of stimulating CNS regeneration is questionable. This review aims to address key developments in the use of NSCs in ALS and evaluate the feasibility of their routine clinical application, with particular focus on stimulating neuronal regeneration.