Advances in stem cell therapy for amyotrophic lateral sclerosis

ABSTRACT

Introduction: Amyotrophic Lateral Sclerosis (ALS) is a progressive, incurable neurodegenerative disease that targets motoneurons. Cell-based therapies have generated widespread interest as a potential therapeutic approach but no conclusive results have yet been reported either from pre-clinical or clinical studies.

Areas covered: This is an integrated review of pre-clinical and clinical studies focused on the development of cell-based therapies for ALS. We analyze the biology of stem cell treatments and results obtained from pre-clinical models of ALS and examine the methods and the results obtained to date from clinical trials. We discuss scientific, clinical, and ethical issues and propose some directions for future studies.

Expert opinion: While data from individual studies are encouraging, stem-cell-based therapies do not yet represent a satisfactory, reliable clinical option. The field will critically benefit from the introduction of well-designed, randomized and reproducible, powered clinical trials. Comparative studies addressing key issues such as the nature, properties, and number of donor cells, the delivery mode and the selection of proper patient populations that may benefit the most from cell-based therapies are now of the essence. Multidisciplinary networks of experts should be established to empower effective translation of research into the clinic.

KEYWORDS:

• Amyotrophic lateral sclerosis
• stem cells
• transplantation
• clinical trials
• animal models
• cellular models

Article Highlights

• In vitro and in vivo preclinical studies demonstrate the efficacy of both neural stem cells and mesenchymal stem cells in targeting pathogenetic mechanisms and slowing disease progression in in vitro and animal ALS models.

• The field lacks experiments in large animal models that better simulate human anatomy and physiology.

• Phase I/II cell-based clinical trials demonstrate the safety of both neural stem cells and mesenchymals stem cells but lack definitive evidence of efficacy in ALS patients. The field strongly requires well-designed, randomized, robust clinical trials.

• The protocols for cellular expansion in most clinical studies are not reported or are suboptimal. Hence, some negative clinical results may be explained by the poor quality of the transplanted cell products.

• Comparative studies addressing main issues such as the types and numbers of cells, the modes of delivery and the appropriate populations of selected patients that might best benefit from cell-based therapies are essential.

• In vivo molecular imaging, advances in tissue engineering and the use of nanomaterials are promising technologies for improving future clinical trials.

• Substantial effort should be made by basic and clinical researchers to communicate to patients and others realistic expectations arising from scientific results. This can eliminate unrealistic hopes that drive the phenomenon of stem cell tourism.

This box summarizes key points contained in the article.

Acknowledgments

The author(s) would like to acknowledge networking support by the COST Action CA16122. DM acknowledges Croatian Science Foundation, project IP-2016-06-9451 and co-financing by the European Union through the European Regional Development Fund, Operational Programme Competitiveness and Cohesion, grant agreement No. KK.01.1.1.01.0007, CoRE - Neuro. LB and AS acknowledge Polish National Centre for Research and Development grant Strategmed No. [1/234261/2/NCBR/2014]. The authors would like to apologize to colleagues whose excellent work could not be cited in this manuscript due to space limitations.

Declaration of Interest

The author(s) would like to acknowledge networking support by the COST Action CA16122.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded.