Research has shown neuroinflammation to have a significant role in the pathogenesis of Parkinson’s disease (PD). Much of this same research has also demonstrated mesenchymal stem cells (MSCs), and specifically, allogeneic bone marrow-derived MSCs, can be effectively used as an immunomodulatory therapy for the potential treatment of PD.
The goal of Schiess et al.’s study was to evaluate the safety and tolerability of first-of-its-kind intravenous allogeneic bone marrow-derived MSCs (allo-hMSCs) in patients with PD.
Neurological disorders continue to be the leading cause of disability-adjusted life years lost worldwide (a statistical measure of years of healthy life lost as a result of death or disability relating to the constitution). While the numbers of those diagnosed with neurological disorders, including stroke, multiple sclerosis, motor neuron disease, and dementia continue to increase at a rapid rate, none are growing as fast as PD.
Considering the rapid progression of progressively intensifying symptoms associated with PD and the relatively poor progress in the discovery of therapies to prevent, or even slow, progression of PD, the authors identified the identification of effective and safe disease-modifying therapies for PD to be a priority.
As part of this study, Schiess et al. studied the peripheral immune system in PD neurodegeneration through the evaluation of LPS rat models, glial cells, and cerebrospinal fluid gathered from patients. As a result of these investigations, the authors determined that an adaptive immune response does contribute to progression supporting the rationale for using MSCs as a potential therapy for PD.
To evaluate the effectiveness of this therapy, Scheiss et al. developed and conducted a single-center, open-label, ascending-dose-escalation phase 1 clinical study involving 20 patients with mild to moderate PD. Participants were assigned to single intravenous doses of 1 of 4 doses and evaluated at weeks 3, 12, 24, and 52 post-infusion.
In addition to evaluating the safety and tolerability of an intravenous infusion of bone marrow-derived allow-hMSCs, the research team also evaluated participants for relevant biomarkers for the mechanism of action and clinical assessment of PD progression.
The authors point out that while there were no serious adverse reactions related to the infusion and no responses to donor-specific human leukocyte antigens, the most commonly reported side effect was dyskinesias and hypertension. Further studies will need to monitor the emergence or exacerbation of post-infusion dyskinesias and hypertension to better understand their occurrence as part of this study.
In conclusion, Sheiss et al. found that a single infusion of allogeneic MSCs ranging from 1 to 10×106 intravenous allo-hMSCs/kg was safe, well tolerated, and not immunogenic in patients with mild-to-moderate PD. The authors also found that peripheral inflammation markers appeared to be reduced at 52 weeks after receiving the highest dose, leading to the conclusion that the highest dose had the most significant effect at the 52-week interval.
Based on these findings, the authors recommend moving forward with a phase 2 randomized, placebo-controlled efficacy trial using allo-hMSCs in a larger population of well-defined Parkinson’s disease patients.
Source: “Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Safety in ….” 27 Mar. 2021, https://movementdisorders.onlinelibrary.wiley.com/doi/full/10.1002/mds.28582.