Neuroprotection for Amyotrophic Lateral Sclerosis: Role of Stem Cells, Growth Factors, and Gene Therapy

Abstract

Various molecular mechanisms including apoptosis, inflammation, oxidative stress, and excitotoxicity have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), though the exact mechanisms have yet to be specified. Furthermore, the underlying restorative molecular mechanisms resulting in neuronal and/or non-neuronal regeneration have to be yet elucidated. Therapeutic agents targeting one or more of these mechanisms to combat either initiation or progression of the disease are under research. Novel treatments including stem cell therapy, growth factors, and gene therapy might prolong survival and delay progression of symptoms. Harnessing the regenerative potential of the central nervous system would be a novel approach for the treatment of motor neuron death resulting from ALS. Endogenous neural replacement, if augmented with administration of exogenous growth factors or with pharmaceuticals that increase the rate of neural progenitor formation, neural migration, and neural maturation could slow the rate of cell loss enough to result in clinical improvement. In this review, we discuss the impact of therapeutic treatment involving stem cell therapy, trophic factors, gene therapy, and combination therapy on disease onset and progression of ALS. In addition, we summarize human clinical trials of stem cell therapy, growth factor therapy, and gene therapy in individuals with ALS.

Therapeutic neuroprotective agents for amyotrophic lateral sclerosis

“…The translational failures may be explained in part by the following: (i) though SOD1 G93A transgenic mice have been the most common model for therapeutic agent studies, there is genetic variation/mutation among ALS patients [172]. To what extent the SOD1 mouse model faithfully represents human ALS disease remains debatable; it may more accurately represent a small fraction of fALS rather than sALS patients [173, 174].…”

Suicidal Behavior and Neurological Illnesses

“…Advances in proteomics, genomics, and metabolomics, and ongoing and planned clinical trials for neurorestoration within the human central nervous system, offer hope for patients suffering from MS, ALS, and for their family members [98,116–118]. …”

Roles of Vascular Endothelial Growth Factor in Amyotrophic Lateral Sclerosis

“…The transplanted stem cells caused a delay in disease progression, prolonged lifespan, promoted survival of motor neurons, and improved neuromuscular function. Neuroprotection resulted partially from the preservation of glutamate transporter GLT-1 levels, reduction of microgliosis, and increase of VEGF and angiopoietin 2 [269, 270]. …”