Cell-based therapies for amyotrophic lateral sclerosis/motor neuron disease

Abstract

Currently, there is a lack of high-quality evidence to guide practice on the use of cell-based therapy to treat ALS/MND.We need large, prospective RCTs to establish the efficacy of cellular therapy and to determine patient-, disease- and cell treatment-related factors that may influence the outcome of cell-based therapy. The major goals of future research should be to determine the appropriate cell source, phenotype, dose, and route of delivery, as these will be key elements in designing an optimal cell-based therapy programme for people with ALS/MND. Future research should also explore novel treatment strategies, including combinations of cellular therapy and standard or novel neuroprotective agents, to find the best possible approach to prevent or reverse the neurological deficit in ALS/MND, and to prolong survival in this debilitating and fatal condition.

Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis

“…The majority of the clinical trials were principally focused on the safety and feasibility of the surgical procedure related to the stem cell implantation. Secondly, these clinical trials were not powered to demonstrate any clinical benefit [ 136 ].…”

“…In 2016, Abdul et al published a systematic review aiming to assess the effectiveness of stem cell therapy in people with ALS, compared with a placebo or no additional treatment [ 136 ]. However, the authors could not identify any randomized controlled trial (RCT), quasi-RCT or cluster RCT involving the use of stem cells in ALS/MND patients.…”

“…However, the authors could not identify any randomized controlled trial (RCT), quasi-RCT or cluster RCT involving the use of stem cells in ALS/MND patients. Thus, there is an absence of high-quality published evidence to assess the safety and efficacy of stem cell transplantation in ALS [ 136 ]. Moreover, when analyzing the single arm phase I/II clinical studies available in the literature, the authors found substantial variability between clinical trials in terms of selection criteria, intervention methods and objective outcomes, with the involvement of small number of participants and a short-term follow-up period [ 136 ] .…”

“…To investigate the long-term safety and efficacy of cellular therapy for ALS, well-designed prospective randomized-controlled trials with larger sample size, long-term-follow up and standardization of cell products, are urgently needed [ 136 ].…”

n‐butylidenephthalide treatment prolongs life span and attenuates motor neuron loss in SOD1G93A mouse model of amyotrophic lateral sclerosis

“…Additionally, although a few novel therapeutic strategies such as cell and gene therapy have been tested for the better treatment of ALS, there are still no definitive and conclusive outcome yet. [7][8][9] Riluzole, the only drug approved by Food and Drug Administration (FDA) of United States, can moderately prolong ALS patients' life span by 2-3 months through the inhibition of the glutamate release, but it may only benefit a subset of patients with ALS. 10,11 Thus, it is indispensable to develop novel therapeutic drugs for this devastating disease.…”