Neural stem cell therapy for neurodegenerative disorders: The role of neurotrophic support

Abstract

Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease currently affect tens of millions of people worldwide. Unfortunately, as the world's population ages, the incidence of many of these diseases will continue to rise and is expected to more than double by 2050. Despite significant research and a growing understanding of disease pathogenesis, only a handful of therapies are currently available and all of them provide only transient benefits. Thus, there is an urgent need to develop novel disease-modifying therapies to prevent the development or slow the progression of these debilitating disorders. A growing number of pre-clinical studies have suggested that transplantation of neural stem cells (NSCs) could offer a promising new therapeutic approach for neurodegeneration. While much of the initial excitement about this strategy focused on the use of NSCs to replace degenerating neurons, more recent studies have implicated NSC-mediated changes in neurotrophins as a major mechanism of therapeutic efficacy. In this mini-review we will discuss recent work that examines the ability of NSCs to provide trophic support to disease-effected neuronal populations and synapses in models of neurodegeneration. We will then also discuss some of key challenges that remain before NSC-based therapies for neurodegenerative diseases can be translated toward potential clinical testing.

Introduction

The potential of cell transplantation as a therapy for neurodegenerative disorders was first examined nearly three decades ago with landmark studies of fetal mesencephalic tissue transplantation in Parkinson's disease (PD) patients (Lindvall et al., 1988). Although these initial studies produced variable results, the field's interest in this approach continued to grow and increasingly focused on the regenerative potential of neural stem cells (NSCs) in the hope that they could provide a renewable and more precise source of cells for transplantation. Building upon preclinical findings from PD models, researchers began to also investigate NSC transplantation for other neurodegenerative conditions including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). As a result the field's understanding of NSC transplantation and the mechanisms by which they influence these disorders has grown immensely. Yet significant challenges remain regarding if and how these promising preclinical findings can be translated into successful clinical trials.