Stem Cell Therapies for Neurological Diseases: The Devil’s in the Details

Stem cell therapies offer a promising approach for immunomodulation, neuroprotection and repair of damaged nervous systems, but they are not yet ready for prime time.

So argued Jeffrey A. Cohen, MD, Director of Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research, at an April 25 “Section Topic Controversies” session on stem cell therapies for neurological diseases at the American Academy of Neurology’s 2017 annual meeting in Boston. In a talk titled “The Devilish Details, Challenges and Uncertainties,” Dr. Cohen presented the more cautionary side of the debate.

“Many stem cell therapies are in various stages of development, each with its own purpose, datasets, risks and efficacies,” Dr. Cohen said. “None should be considered standard care at this time.”

Most of the session centered on two approaches (summarized below) that have received the most attention for multiple sclerosis (MS), a disease on which Dr. Cohen has published and presented at international conferences. He emphasized, however, that the concepts debated are generally applicable to other stem cell therapies and for other neurological diseases, including Parkinson’s disease, Huntington’s disease and traumatic brain injury.

Immunoablation and hematopoietic stem cell (HSC) transplantation

Immunoablation followed by infusion of autologous HSCs can be viewed as a potent anti-inflammatory strategy for rebooting the immune system. Evidence to date shows that the therapy is long-lasting, based on up to seven years’ worth of longitudinal data in patients with MS.

But Dr. Cohen, who also serves as Director of Cleveland Clinic’s Experimental Therapeutics Program, advised caution to his colleagues before they consider offering this therapy, for the following reasons:

• Risk is not insignificant. Risk of death from the HSC transplant portion of the protocol has been declining with experience, but it still runs at about 1 to 2 percent.
• Patient selection is critical. This therapy offers anti-inflammatory benefits only; it does not repair neural injury and thus is not indicated for the progressive forms of MS.
• This is not to be ‘tried at home.’ Only a major healthcare center with extensive experience in performing HSC transplantation and managing MS should attempt this therapy.
• Head-to-head trials are needed. Whether this approach should be regarded as a reasonable alternative to standard potent anti-inflammatory treatment options — rather than a last resort — has yet to be evaluated in clinical trials.

Enhanced endogenous cell therapy, including mesenchymal stem cells

Stem cells can be recruited to repair damaged nervous tissue, offering an exciting potential avenue of therapy for patients with progressive forms of MS as well as other conditions in which neural injury has occurred.

Dr. Cohen, who has been involved in early-phase studies of repair-promoting stem cell therapies, emphasized that such therapies are still in the experimental stages for MS and other neurological diseases, and it is premature to offer them in clinical practice. Although some safety studies have been completed with good results, the therapies’ benefits have yet to be proven in clinical trials.

The lack of evidence for efficacy has not stopped some freestanding clinics from offering this therapy directly to patients who are desperate for an alternative treatment option and willing to try “medical tourism.” As for all clinical cell-based therapies, rigorous quality and safety control in cell production is critical, which makes seeking treatment from commercial clinics in countries where medical facilities might be poorly regulated especially worrisome.

Dr. Cohen touched on some fundamental questions that have yet to be answered:

• Which mesenchymal stem cells (MSCs) are best? Whether MSCs obtained from different tissue sources (e.g., adipose tissue or bone marrow) have identical restorative properties has not yet been determined.
• How many cells are needed for therapy? The dose currently under consideration as optimal for therapeutic benefit is so high that producing it for clinical use is not possible at this time.
• What is the most effective route of administration?
• How should cells be treated in terms of cryopreservation and thawing?
• Will repeated transplantation be required to sustain benefit? This appears likely, as some evidence indicates that MSCs do not persist in tissues.

“It can be argued that it’s even too early to have clinical trials on these therapies,” Dr. Cohen cautioned. “No one really knows how these treatments should be performed.”

The bottom line

Cell-based treatments for neurological diseases are now in various phases of clinical trials and offer high hopes of potential benefits for disease-modifying and restorative therapy, Dr. Cohen concluded. He added, however, that much work remains in defining their therapeutic roles relative to existing therapies, identifying appropriate candidate populations and sorting out the logistics of a new treatment paradigm.

Image at top: Characteristic morphology of mesenchymal stem cells in culture.