An update on stem cell therapy and its use in neurological disease was presented at the 2019 American Academy of Neurology Annual Meeting in Philadelphia, PA. Several faculty speakers discussed patient cases, a review of the basic science of stem cell therapy, recent studies, insights about stem cell tourism, and projections about where stem cell treatment for neurological disease is headed. Paul M. George, MD, PhD, MSE, Sean I. Savitz, MD, Jaime Imitola, MD, FAAN, and Antonio M. P. Omuro, MD, presented talks followed by a question and answer session.
Benefits of cell therapy
The group explained that several different modes of stem cell therapy delivery are used in treating neurological conditions, including intravenous, intra-arterial, intracerebral, and intrathecal. One of the points mentioned is that the term stem cell therapy is often discussed, and that cell therapy includes stem cell therapy as well as other types of cells.
Cell therapy has been used in the research setting to treat several neurological conditions, including stroke, multiple sclerosis, and Parkinson disease. The speakers explained that cell therapy could benefit neurological disease through a number of mechanisms, but not necessarily by “growing new nerves.” Effects of cell therapy include neuroprotection, anti-inflammatory effects, and immunomodulatory effects.
Cell therapy for stroke
Under normal circumstances, the post-ischemic brain shows effects of peripheral inflammation. Cell therapy in the stroke setting is believed to alter this response through an immunomodulatory effect.
The MASTERS trial, which evaluated the effects of intravenous cellular therapy in the setting of acute stroke, was discussed.1 This trial was a randomized, double-blind, placebo-controlled, dose-escalation trial of intravenous multipotent adult progenitor cells. Patients received either placebo or multipotent adult progenitor cells. The therapy was well tolerated, without adverse effects. There was no difference in the primary endpoint at 90 days, but there was a difference at 1 year. The difference was greater among patients who received the treatment within 24 hours. This suggests that there is potential benefit of stem cell therapy in the treatment of acute stroke, and that timing of the therapy needs to be taken into consideration.
Cell therapy for Parkinson disease
Cellular therapy in Parkinson disease may work differently. Unlike the acute and evolving changes of acute stroke, Parkinson disease is characterized by chronic degenerative changes in the CNS. SB623 is a cell therapy derived from bone marrow mesenchymal stem cells (MSCs) that has immunosuppressive and angiogenic effects. A study using intracranial injection of SB623 gene modified MSCs in Parkinson disease was discussed. Patients met the primary endpoint and improved from their baseline.
The take-home message
The take-home message of the talks and the question and answer session was that stem cells don’t necessarily need to be administered to the target tissue because the therapy affects inflammation, a major cause of the neurological damage. Intravenous administration of bone marrow and adipose derived stem cell therapies are approaches that are moving forward in human clinical trials.
However, stem cell tourism, an approach that is being used among some patients, can result in adverse effects, including tumors. Many clinics offer this type of therapy, and patients who are dissatisfied with their prognosis may seek treatment, which isn’t always safe or effective. Nevertheless, the immunomodulatory effect of intravenous administration can have a beneficial effect on acute disease and may show benefits in chronic disease as well. More research needs to be done to establish safety and efficacy, as well as optimal timing for therapy.
1. Hess DC, Wechsler LR, Clark WM, et al. Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2017;16:360-368. doi: 10.1016/S1474-4422(17)30046-7.