Cell therapy and stem cells in animal models of motor neuron disorders

Abstract

Amyotrophic lateral sclerosis (ALS), spinal bulbar muscular atrophy (or Kennedy's disease), spinal muscular atrophy and spinal muscular atrophy with respiratory distress 1 are neurodegenerative disorders mainly affecting motor neurons and which currently lack effective therapies. Recent studies in animal models as well as primary and embryonic stem cell models of ALS, utilizing over-expression of mutated forms of Cu/Zn superoxide dismutase 1, have shown that motor neuron degeneration in these models is in part a non cell-autonomous event and that by providing genetically non-compromised supporting cells such as microglia or growth factor-excreting cells, onset can be delayed and survival increased. Using models of acute motor neuron injury it has been shown that embryonic stem cell-derived motor neurons implanted into the spinal cord can innervate muscle targets and improve functional recovery. Thus, a rationale exists for the development of cell therapies in motor neuron diseases aimed at either protecting and/or replacing lost motor neurons, interneurons as well as non-neuronal cells. This review evaluates approaches used in animal models of motor neuron disorders and their therapeutic relevance.