Cell therapies hold great promise and rise enthusiasm in neurological disorders. They are supposed to act not only through replacing dead cells, but also through releasing protective factors and/or exerting immunomodulatory and neuroprotective functions. Because of the limited treatment options for progressive multiple sclerosis (PMS), cellular therapies are considered as possible treatment options for PMS.
STEMS is the first a prospective, therapeutic exploratory, non-randomized, open-label, single-dose-finding phase 1 clinical trial (NCT03269071) (Genchi et al., 2023). hfNPCs were administered to twelve probands with 10–22 years of disease duration and severe disabilities. They were ineligible for any alternative disease-modifying therapies. Patients received tacrolimus and oral prednisolone (Genchi et al., 2023) to prevent rejection.
No severe adverse reaction related to the cell therapy were reported, and the primary endpoints have been met. MRI brain and grey matter volume measurements showed lower rates of total brain and grey matter atrophy in the participants injected with the highest dose of hfNPCs (Fossati et al., 2023). Unexpectedly, Genchi et al. found quite high MRI-based disease activity, with new T2 lesions (6/12) of which half were contrast-enhancing (Genchi et al., 2023). The interpretation of the result is challenging, because there were no annual radiological assessment performed at baseline. The cerebrospinal fluid of the transplanted patients showed increased levels of anti-inflammatory and neuroprotective molecules, although these should be interpreted with caution due to the immune suppression therapy (Fossati et al., 2023).
STEMS is a step forward in terms of independent phase I cell-based therapies studies in MS. This study shows that cell-based therapies are safe in PMS and encourages to perform of further multicenter studies to establish the efficacy of cell-therapies (Fossati et al., 2023).
- Genchi et al. reported the first single-center phase 1 clinical trial assessing safety of intrathecally transplanted human fetal neural progenitor cells (hfNPCs) in progressive multiple sclerosis (PMS).
- During the 2-year follow-up, there were no severe adverse reactions related to the cell therapy.
- This study shows that cell-based therapies are safe in PMS and encourages to perform of further multicenter studies to establish the efficacy of cell-therapies.
- Fossati V, Peruzzotti-Jametti L, Pluchino S. A neural stem-cell treatment for progressive multiple sclerosis. Nat Med. 2023 Jan;29(1):27-28. doi: 10.1038/s41591-022-02164-9. PMID: 36639562.
- Genchi A, Brambilla E, Sangalli F, et al. Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study. Nat Med. 2023;29(1):75-85. doi:10.1038/s41591-022-02097-3
- Magdalena Mroczek, Center for Cardiovascular Genetics & Gene Diagnostics, Foundation for People with Rare Diseases, Schlieren-Zurich 8952, Switzerland
- Marina Boziki, Laboratory of Experimental Neurology and Neuroimmunology and Multiple Sclerosis Center, 2nd Neurological University Department, AHEPA General Hospital of Thessaloniki, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
Publish on behalf of the Scientific Panel on Neuroscience/Translational neurology