Cord blood as a potential therapeutic for amyotrophic lateral sclerosis

ABSTRACT

Introduction: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration in the brain and spinal cord. Treatment options are limited due to the complexity of underlying disease factors. Cell therapy, using human umbilical cord blood (hUCB) cells may be a promising new treatment for ALS, mainly by providing a protective microenvironment for motor neuron survival.

Areas covered: Composition, in vitro and in vivo differentiation of hUCB cells, and the advantages of cord blood as a source of transplant cells are discussed. A brief history of hUCB in treatment of an ALS animal model and the feasibility of these cells in therapy for ALS patients is provided. Current ALS clinical trials are also deliberated.

Expert opinion: Among multiple advantages, hUCB cells’ production of various anti-inflammatory/growth/trophic factors makes them an attractive cell source for ALS therapy. Biodistribution and optimal hUCB cell dose for transplantation have been determined in preclinical studies. Repeated intravenous cell doses during disease progression may be the best approach for cell-based ALS treatment. Accumulated evidence shows the efficacy of naïve or genetically modified MNC hUCB cells in the treatment of ALS and provide a superior basis for the development of clinical trials in the near future.

KEYWORDS:

• Human umbilical cord blood
• multipotency
• ALS
• treatment
• neuroprotection

Article highlights

• Cell therapy is a promising treatment for ALS

• Human umbilical cord blood (hUCB) may be preferable to other cell sources and has multiple advantages that make it an attractive source of transplantable cells for the treatment of ALS

• Intravenous mononuclear hUCB (MNC hUCB) cell transplantation into pre-symptomatic ALS mice showed delayed disease progression and prolonged mouse lifespan

• Neuroprotective and/or trophic effects of MNC hUCB cells were detected by post-transplant cell biodistribution and optimal cell dose was determined

• Repeated administration of smaller MNC hUCB cell doses into symptomatic ALS mice demonstrated that cell treatment, even when initiated at the symptomatic disease stage, could improve disease outcomes by providing ongoing protection for motor neurons

• Genetically modified MNC hUCB cells over-expressing various therapeutic growth factors significantly increase neuroprotective cell transplant effects

• Accumulating evidence of the efficacy MNC hUCB cells in the treatment of ALS provides a superior basis for its use in the development of clinical trials

Declarations of interest

S. Garbuzova-Davis is a consultant, J. Ehrhart is Director of Research and Development, and P. R. Sanberg is a co-founder of Saneron CCEL Therapeutics Inc. S. Garbuzova-Davis and P.R. Sanberg hold patents for the treatment of neurodegenerative diseases using hUCB cells. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This review was supported by the Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair at the University of South Florida. S. Garbuzova-Davis is funded by the National Institutes of Health (1R01 NS090962-01).