Stem cell treatments for amyotrophic lateral sclerosis: a critical overview of early phase trials

ABSTRACT

Introduction: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of cortical, brainstem, and spinal motor neurons; it causes progressive muscle weakness and atrophy, respiratory failure, and death. No currently available treatment either stops or reverses this disease. Therapeutics to slow, stop, and reverse ALS are needed. Stem cells may be a viable solution to sustain and nurture diseased motor neurons. Several early-stage clinical trials have been launched to assess the potential of stem cells for ALS treatment.

Areas covered: This review covers the key advances from early phase clinical trials of stem cell therapy for ALS and identifies promising avenues and key challenges.

Expert opinion: Clinical trials in humans are still in the nascent stages of development. It will be critical to ensure that powered, well-controlled trials are conducted, that optimal treatment windows are identified, and that the ideal cell type, cell dose, and delivery site and method are determined. Several trials have used more invasive procedures, and ethical concerns of sham procedures on patients in the control arm and on their safety should be considered.

KEYWORDS:

• Amyotrophic lateral sclerosis
• ALS
• clinical trial
• preclinical
• stem cells
• therapy

View correction statement:

Correction

Article highlights

• There is no cure for ALS despite numerous clinical trials; current therapies are palliative and only extend survival a few months.

• Stem cell therapy is considered an attractive approach for ALS that addresses the complex disease pathogenesis through multiple potential mechanisms.

• The premise of stem cell therapy for ALS is based on improving the diseased microenvironment. While stem cells are unable to directly replace diseased motor neurons, transplanted stem cells secrete neurotrophic factors and differentiate into supportive cells, such as astrocytes and microglia, generating a neuroprotective milieu that can slow degeneration of motor neurons.

• Encouraging results in preclinical animal models advocated human clinical trials.

• Several stem cell sources, cell doses, and methods of delivery are presently being evaluated in early phase clinical trials. Determination of an optimal window of treatment will also aid endeavors to identify promising treatment options.

• Most current clinical trials are assessing safety as their primary objective. However, 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, but ethical implications should be considered.

Declaration of interest

The authors have no 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.

Reviewer disclosures

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

Additional information

Funding

The work of the authors is supported by the Program for Neurology Research & Discovery, the A. Alfred Taubman Medical Research Institute, the Sinai Medical Foundation, the Katherine Rayner Fund, and the National Institutes of Health [K23 ES027221].