Stem cells: comprehensive treatments for amyotrophic lateral sclerosis in conjunction with growth factor delivery.
Amyotrophic lateral sclerosis (ALS) is characterized by loss of both upper and lower motor neurons. ALS progression is complex and likely due to cellular dysfunction at multiple levels, including mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress, axonal dysfunction, reactive astrocytosis, and mutant superoxide dismutase expression, therefore, treatment must provide neuronal protection from multiple insults. A significant amount of ALS research focuses on growth factor-based therapies. Growth factors including insulin-like growth factor-I, vascular endothelial growth factor, brain-derived neurotrophic factor, and glial-derived neurotrophic factor exhibit robust neuroprotective effects on motor neurons in ALS models. Issues concerning growth factor delivery, stability and unwanted side effects slow the transfer of these treatments to human ALS patients. Stem cells represent a new therapeutic approach offering both cellular replacement and trophic support for the existing population. Combination therapy consisting of stem cells expressing beneficial growth factors may provide a comprehensive treatment for ALS.
Lunn
J Simon
JS
Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA.
Hefferan
Michael P
MP
Marsala
Martin
M
Feldman
Eva L
EL
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000628:therapy; D001369:Axons / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D009046:Motor Neurons / Q000166:cytology* / Q000502:physiology; D018384:Oxidative Stress; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
D036341:Intercellular Signaling Peptides and Proteins