Effect of stem cell treatment on functional recovery of spinocerebellar ataxia: systematic review and meta-analysis

Abstract

Background Spinocerebellar ataxia is a hereditary neurodegenerative disease characterized by changes in balance, locomotion and motor coordination. Stem cell therapies are currently being investigated as an alternative to delay the evolution of the disease, and some experimental studies have investigated the effect of stem cell treatment on spinocerebellar ataxia. Objectives The aim of this review was to investigate whether the application of stem cells produced an effect on functional recovery in individuals with spinocerebellar ataxia. Methods The studies included in this review investigated the efficacy and safety of a protocol for the application of mesenchymal stem cells extracted from umbilical cord and adipose tissue. Two studies used intrathecal route for application and one study used intravenous route. Results Studies have shown clinical improvement in the scores of the ICARS (International Cooperative Ataxia Rating Scale), ADL (Activities of Daily Living Scale), BBS (Berg Balance Scale) and SARA (Scale for the Assessment and Rating of Ataxia), but lacked statistical significance. Conclusions There was low evidence for recommending stem cell therapy in individuals with spinocerebellar ataxia, and no statistical difference was observed for improving functional recovery of patients. Further studies are needed with different designs, largest sample sizes and placebo control, to fully understand anticipated outcomes of cellular therapy for spinocerebellar ataxia.

Preclinical Assessment of Mesenchymal-Stem-Cell-Based Therapies in Spinocerebellar Ataxia Type 3

“…Previous clinical trials in SCA patients reported the need for further detailed investigations of the molecular transformation of MSCs, in order to clarify the maximal passaging numbers that will ensure the long-term safety of hMSC therapy, and to elucidate the therapeutic mechanism [26,35,69]. This highlights the urgency of the need for readjustments in the protocols to improve treatment efficacy in the trials that are underway (http://www.clinicaltrials.gov, NCT01360164, NCT01489267, NCT01958177, NCT02540655, NCT03378414; accessed on 25 July 2021), as well as for the harmonization of the protocols used and, possibly, the formulation of guidelines for these trials, favoring higher sample sizes and reducing the risk of potential bias [69].…”

“…Previous clinical trials in SCA patients reported the need for further detailed investigations of the molecular transformation of MSCs, in order to clarify the maximal passaging numbers that will ensure the long-term safety of hMSC therapy, and to elucidate the therapeutic mechanism [26,35,69]. This highlights the urgency of the need for readjustments in the protocols to improve treatment efficacy in the trials that are underway (http://www.clinicaltrials.gov, NCT01360164, NCT01489267, NCT01958177, NCT02540655, NCT03378414; accessed on 25 July 2021), as well as for the harmonization of the protocols used and, possibly, the formulation of guidelines for these trials, favoring higher sample sizes and reducing the risk of potential bias [69]. From the lessons we have learned from the completed clinical trials, and because this and other preclinical studies suggest that a multiple MSC transplantation regimen could be a promising therapeutic strategy for the treatment of SCA3/MJD, it is imperative to address some concerns, such as (1) the possible risks of repeated (and systemic) transplantation, (2) defining the least invasive and effective route of administration, (3) determining which types of cells offer the best potential to treat this particular disease, (4) anticipating patients' responses to treatments according to disease course, (5) defining the predicted actions of stem cells and the outcomes to be expected, and (6) establishing the therapeutic value of hMSC transplantation at a post-symptomatic stage.…”

Mesenchymal stem cells for lysosomal storage and polyglutamine disorders: Possible shared mechanisms

“…One of the major limitations of using MSC to correct the nervous system is their poor survival in unfriendly environments and consequent need to use repeated treatments 7‐11 . In one of our studies, we assessed for the levels of hepatic aminotransferases after repeated transplantation and these were not increased when compared to nontreated or WT mice, indicating absence of liver toxicity in treated mice 8 .…”

“…6 Clinical trials have demonstrated that MSC are safe and promote a favourable course of the disease, but their effects are not as long-lasting as desirable due to poor survival in inhospitable environments or inappropriate therapeutic dosage. [7][8][9][10][11] Researchers have been suggesting ways of counteracting their low endurance with pre-conditioning protocols. 12 Moreover, the use of MSC whole secretome or secreted extracellular vesicles is also being evaluated as valuable alternatives.…”

Regenerative Neurology and Regenerative Cardiology: Shared Hurdles and Achievements

“…They were demonstrated to be safe but their effects were not always consistent, as preclinical studies suggested. This may be due to poor survival in disease environments and/or because inappropriate therapeutic dosage and route of delivery or inconsistent trial design [ 162 , 163 , 164 , 165 ].…”