![]() ![]() Intravenously to irradiated SOD1 G93A mice, which delayed the onset of motor symptoms and extended overall survival. In an early seminal report, human umbilical cord blood (hUCB) was administered Mutant SOD1 animals capture the salient features of ALS, including selective MN degenerationĬoncurrent with muscle atrophy and motor dysfunction. SOD1 was the first identified ALS gene and remains among the more prevalent ALS mutations. The majority of preclinical stemĬell studies have been performed in mouse and rat ALS models expressing mutant superoxide dismutase 1 (SOD1). Potential benefit of stem cell therapy for ALS, since they served as the stimulus for human trials. , it is worth mentioning the pivotal preclinical studies that demonstrated the While a comprehensive analysis of preclinical studies is outside the scope of this review and has been previously addressed They also revealed mechanismsīy which stem cells could improve the MN microenvironment in ALS by the “neighborhood” approach, identifying platformsįrom which to launch more promising approaches in human clinical trials.ģ. Preclinical animal studies of stem cell therapy for ALS Preclinical studies in this vein inĪnimal models were encouraging and demonstrated the potential applicability of stem cells to treat ALS. Modulatory neurons that synapse with diseased MNs. ![]() Transplanted stem cells in thisĬapacity secrete neurotrophic factors, differentiate into non-diseased, non-neuronal cells, such as astrocytes and microglia, or into Where transplanted stem cells adopt a supportive role by providing a nurturing, neuroprotective microenvironment that amelioratesĭetrimental conditions for diseased MNs, thereby slowing neurodegeneration and neuronal death. Need to project axons, frequently over significant distances, and synapse with endogenous neurons and muscle, all the while enduring aįor these reasons, the field has reformulated the approach into a “neighborhood theory” of stem cell therapy, In order to integrate seamlessly with preexisting neural circuits, transplanted stem cell-derived MNs Therapy was to employ ESCs or PSCs to generate MNs for transplantation into ALS patients. Neural progenitor cells (NPCs) are PSCs that can differentiate into neuronal or glial cells Embryonic stem cells (ESCs) are totipotent and canĭifferentiate into any cell type, while pluripotent stem cells (PSCs) can differentiate into more limited, specific cell types. When they divide, the parent cell retains stemness while theĭaughter cell can differentiate. Possess the ability to self-renew and maintain an undifferentiated state. Stem cells were originally proposed as an ALS treatment to replenish the populations of progressively lost MNs. Multiple potential mechanisms, and encouraging preclinical studies have justified early phase clinical trials in humans. Stem cell therapy is considered an attractive route that directly addresses the loss of MNs through One-solution-fits-all approach may be challenging, which has been borne out by the lack of successful trials to date. The heterogeneity of ALS, both from a molecular standpoint and clinical phenotype, suggests that a pharmacological There is no cure for ALS theįood and Drug Administration (FDA) has approved riluzole, a putative glutamate receptorĪntagonist, and edaravone, a possible free radical scavenger, which produce modest benefits. ![]() Theĭisease exhibits clinical and pathophysiologic heterogeneity both familial and sporadic cases occur, and the underlying genetic causeĪlso varies, although mutations to C9ORF72, SOD1, TARDBP, and FUSĪre the most common. Subpopulations exhibit above average incidence. The incidence of ALS ranges from 1 to 4 cases per 100,000, although some Individuals, and up to 15% of persons with ALS manifest frontotemporal dementia due to neuronal dysfunction in the prefrontal and Changes in executive function are common and occur in up to 50% of (MNs) that leads to skeletal muscle weakness and atrophy, with death typically resulting from respiratory failure 2 to 4 years afterĭisease diagnosis. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of cortical, brainstem, and spinal motor neurons ![]()
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