Potential of Cellular Therapy for ALS: Current Strategies and Future Prospects

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive upper and lower motor neuron (MN) degeneration with unclear pathology. The worldwide prevalence of ALS is approximately 4.42 per 100,000 populations, and death occurs within 3–5 years after diagnosis. However, no effective therapeutic modality for ALS is currently available. In recent years, cellular therapy has shown considerable therapeutic potential because it exerts immunomodulatory effects and protects the MN circuit. However, the safety and efficacy of cellular therapy in ALS are still under debate. In this review, we summarize the current progress in cellular therapy for ALS. The underlying mechanism, current clinical trials, and the pros and cons of cellular therapy using different types of cell are discussed. In addition, clinical studies of mesenchymal stem cells (MSCs) in ALS are highlighted. The summarized findings of this review can facilitate the future clinical application of precision medicine using cellular therapy in ALS.

Molecular mechanisms and therapeutic strategies for neuromuscular diseases

“…Preclinical findings support this, and ongoing phase I and II clinical trials in ALS patients indicate positive results in safety and tolerability. However, substantial improvements for ALS patients necessitate continued collaboration between basic and clinical researchers [ 67 , 68 ].…”

Motor neuron disease in a patient with overlap syndrome (rheumatoid arthritis; systemic lupus erythematosus, Sjogren’s syndrome)

“…They found that serum C4 levels in ALS patients were lower than in the healthy control group [ 33 ]. Depending on the understanding of the role of the immune system in motor neuron diseases and the developments in drug technology, some studies investigating the effectiveness of immune modulator biological agents in the treatment of motor neuron disease have started [ 34 , 35 ].…”

Therapeutic Potential of Exosomes Derived from Adipose Tissue-Sourced Mesenchymal Stem Cells in the Treatment of Neural and Retinal Diseases

“…Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results in the progressive loss of motor neurons in the brain and spinal cord [43]. An increased aggregation of superoxide dismutase 1 (SOD1), decreased phosphorylation of cyclic adenosine mono phosphate-response element-binding protein (CREB) and reduced activation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) lead to the development of mitochondrial dysfunction, which is frequently observed in patients suffering from ALS [43]. Accordingly, restoration of mitochondrial function is an important therapeutic goal in the treatment of ALS [43].…”

“…An increased aggregation of superoxide dismutase 1 (SOD1), decreased phosphorylation of cyclic adenosine mono phosphate-response element-binding protein (CREB) and reduced activation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) lead to the development of mitochondrial dysfunction, which is frequently observed in patients suffering from ALS [43]. Accordingly, restoration of mitochondrial function is an important therapeutic goal in the treatment of ALS [43]. Lee and colleagues showed that AT-MSC-Exos attenuated aggregation of SOD1, induced phosphorylation of CREB, and activated PGC-1α, which resulted in the restoration of mitochondrial function [44].…”