Mesenchymal Stem Cell-Derived Neural Progenitors in Progressive MS

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that can take different forms: relapsing-remitting (RRMS), secondary progressive (SPMS), and primary progressive (PPMS). In RRMS, symptoms flare up and then ease, largely due to inflammation, and there are many therapies to manage these relapses. In SPMS and PPMS, the disease gradually progresses without relapses, leading to accumulating disability. Treatments for these progressive forms are limited, and the therapies available are generally less effective than for RRMS.

In this study, Harris et al. explores the use of stem cell-based treatment, specifically mesenchymal stem cell-derived neural progenitors (MSC-NPs), for people with progressive MS. 

MSC-NPs are cells derived from a patient’s own bone marrow and have potential regenerative and immune-modulating effects. Early research suggests that MSC-NPs can provide beneficial effects in animal models of MS. 

This clinical trial was initiated to test the safety and early efficacy of MSC-NPs when injected directly into the spinal fluid of patients with progressive MS. Specifically, Harris et al. wanted to see if these patients would experience fewer or slower disease-related declines after receiving repeated injections of MSC-NPs. 

Evaluating Safety and Early Efficacy Trends

According to the authors, this study found that repeated injections of MSC-NPs were generally safe. Over the two-year follow-up period, no serious side effects were reported by any of the patients. A minor headache was reported by one patient, which did not require treatment, and some other minor issues were reported but were deemed unrelated to the study treatment. 

This confirms the long-term safety of MSC-NPs, which is critical as cell therapies become more widely tested for neurological diseases like MS.

While Harris et al.’s study was not designed to determine whether MSC-NPs were definitively effective, some additional trends were observed:

• Patients with lower levels of disability at the start of the study tended to show more improvement in their mobility and overall functioning than those with higher disability scores.
• Most patients who benefited were those who could still walk when they started the trial, suggesting MSC-NP therapy might be more effective in people with less advanced disability.
• Of the three patients with primary progressive MS, two showed stable disability scores over the two years following treatment. However, the sample size was too small to draw firm conclusions on its effects in PPMS compared to SPMS.

While these findings are promising, the study has significant limitations. With only 20 patients, the study was too small to determine definitive efficacy, so a larger, placebo-controlled trial is necessary to confirm any potential benefits of MSC-NPs. 

Additionally, the open-label design, where both patients and researchers knew who was receiving the treatment, could mean that some effects may have resulted from a placebo response rather than the treatment itself. Furthermore, the therapy may be more effective for patients with lower disability scores, but more research is required to identify which patients are the most suitable candidates for MSC-NP treatment.

Future Directions for MSC-NP Therapy in Progressive MS

Harris et al.’s study has laid the groundwork for further research by establishing MSC-NPs as a safe treatment option over a two-year period. Based on these findings, a larger Phase II trial is underway, involving 50 patients who will receive MSC-NP injections or a placebo over an extended period. This trial will be double-blinded (neither patients nor researchers will know who is receiving the treatment) to give more definitive answers about MSC-NP’s effects on progressive MS.

In summary, MSC-NPs appear to be a safe treatment option for people with progressive MS, with some early evidence suggesting potential benefits in reducing disability for those with less advanced disease. These findings contribute to the understanding of cell-based therapies in MS and support further exploration of MSC-NPs in larger, controlled studies. While MSC-NPs offer hope for future therapies, the authors call for more rigorous research to clarify their impact on long-term disease progression and patient quality of life.

Source:  Harris VK, Stark JW, Yang S, Zanker S, Tuddenham J, Sadiq SA. Mesenchymal stem cell-derived neural progenitors in progressive MS: Two-year follow-up of a phase I study. Neurol Neuroimmunol Neuroinflamm. 2020 Dec 4;8(1):e928. doi: 10.1212/NXI.0000000000000928. PMID: 33277427; PMCID: PMC7738177.