Overview of stem cells therapy in amyotrophic lateral sclerosis

ABSTRACT

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of upper and lower motor neurons with high burden on society. Despite tremendous efforts over the last several decades, there is still no definite cure for ALS. Up to now, only two disease-modifying agents, riluzole and edaravone, are approved by U.S. Food and Drug Administration (FDA) for ALS treatment, which only modestly improves survival and disease progression. Major challenging issues to find an effective therapy are heterogeneity in the pathogenesis and genetic variability of ALS. As such, stem cell therapy has been recently a focus of both preclinical and clinical investigations of ALS. This is because stem cells have multifaceted features that can potentially target multiple pathogenic mechanisms in ALS even though its underlying mechanisms are not completely elucidated. Methods & Results: Here, we will have an overview of stem cell therapy in ALS, including their therapeutic mechanisms, the results of recent clinical trials as well as ongoing clinical trials. In addition, we will further discuss complications and limitations of stem cell therapy in ALS. Conclusion: The determination of whether stem cells offer a viable treatment strategy for ALS rests on well-designed and appropriately powered future clinical trials. Randomized, double-blinded, and sham-controlled studies would be valuable.

KEYWORDS:

• Amyotrophic lateral sclerosis
• als
• stem cell therapy
• clinical trials
• stem cells

Highlights

• Even though many clinical trials have been conducted so far, there is no cure for ALS. Current treatments are palliative and only prolong survival by a few months.

• Stem cells therapy is seen as an attractive approach for ALS to address this complex etiology through multiple potential mechanisms.

• Stem cells cannot directly replace affected motor neurons, but transplanted stem cells secrete neurotrophic factors, differentiate into supporting cells such as astrocytes and microglia, and delay the degeneration of motor neurons.

• Valid research results in animal models have proposed human clinical trials.

• Several stem cells sources, cell doses, and methods of delivery are presently being evaluated in early phase clinical trials.

• The determination of whether stem cells offer a viable treatment strategy for ALS rests on well-designed and appropriately powered future clinical trials. Randomized, double-blinded, and sham-controlled studies would be valuable.

Disclosure statement

The authors declare no conflict of interest in relation to the submitted manuscript.

Authors contribution

MG: conception, organization, literature review, and execution of research project; revising of the first draft of manuscript, review and critique of the manuscript. GJ: literature review and execution of research project; writing of the first draft of manuscript and preparing the tables. KK: execution of research project; review and critique of the manuscript; preparing the first draft of paper’s figures.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Notes on contributors

Goun Je

Goun Je, MD, PhD, is currently a third-year neurology resident at University of Massachusetts Medical Center, USA.

Kiandokht Keyhanian

Kiandokht Keyhanian, MD, is currently a fourth-year neurology resident at University of Massachusetts Medical Center, USA.

Mehdi Ghasemi

Mehdi Ghasemi, MD, is an Associate Program Director and Assistant Professor of Neurology and clinician-scientist at University of Massachusetts Medical Center, USA, with subspecialty in Neuromuscular Medicine from Harvard University. He has over 15 years of research experience in the fields of neuropharmacology, neurodegenerative diseases, and neuromuscular disorders.