Progressive multiple sclerosis (PMS) is a complex, disabling form of multiple sclerosis characterized by the progressive accumulation of central nervous system (CNS) damage. This damage arises from chronic inflammation, demyelination, axonal injury, neuronal degeneration, and gliosis, affecting both white and gray matter in the brain and spinal cord. Despite advancements in MS research, effective reparative therapies for reversing the functional impairments associated with PMS remain largely unavailable.
A promising new approach for PMS treatment is NurOwn, a therapy based on mesenchymal stem cell-derived neurotrophic factor (MSC-NTF) cells. NurOwn utilizes a proprietary method to isolate and culture autologous (self-derived) mesenchymal stem cells (MSCs) from bone marrow. These MSCs are then differentiated to secrete high levels of neurotrophic factors (NTFs), which are believed to have both neuroprotective and immunomodulatory properties. Preclinical studies and early clinical trials have suggested that MSC-NTF therapy could help reduce CNS inflammation and promote neuronal repair mechanisms in PMS patients.
Cohen et al.’s open-label phase II study was conducted to evaluate safety/efficacy of three intrathecal cell treatments
Safety and Tolerability of MSC-NTF Therapy
In this Phase II clinical trial (BCT-101), the safety of MSC-NTF therapy was evaluated in 20 participants with PMS, of whom 18 received treatment. While most participants tolerated the therapy well, two discontinued due to adverse events related to the procedure, including mild symptoms such as coldness, muscle weakness, and fever, as well as one case of arachnoiditis -a rare inflammation of the arachnoid membrane surrounding the spinal cord.
For both affected individuals, MRI scans revealed characteristic lumbar nerve root clumping. Treatment with epidural cortisone and analgesics provided symptom relief, with one participant’s symptoms resolving fully. Importantly, there were no recorded deaths or adverse events associated with MS relapses, and no clinically significant alterations were observed in blood, urinalysis, or vital sign parameters after dosing.
According to the authors, these results highlight the potential tolerability of MSC-NTF therapy, though further studies are required to assess long-term safety.
Potential of MSC-NTF Therapy for PMS
NurOwn’s MSC-NTF cells have been tested in animal models relevant to PMS, including studies on autoimmune encephalomyelitis and optic nerve damage, which have shown the therapy’s potential to reduce inflammation and support neuroprotective mechanisms.
Current studies suggest that intrathecal (spinal) administration may offer unique benefits over intravenous administration by directly addressing meningeal inflammation and delivering neurotrophic factors close to the site of CNS damage. The capability of MSC-NTF cells to modulate inflammation and potentially promote endogenous repair makes it a promising therapeutic modality in PMS.
Functional and Biomarker Outcomes
Cohen et al.’s phase II study used several functional outcomes to assess MSC-NTF efficacy in PMS, including the timed 25-foot walk test (T25FW), nine-hole peg test (9-HPT), low-contrast letter acuity (LCLA), and symbol digit modalities test (SDMT).
Results indicated positive trends in these measures, suggesting that MSC-NTF therapy could improve mobility, hand function, and cognitive speed in PMS patients. Additionally, patient-reported outcomes, such as the MS Walking Scale-12 (MSWS-12), demonstrated improvements in walking function.
Biomarker analysis revealed reductions in cerebrospinal fluid (CSF) inflammatory markers, including MCP-1, sCD27, SDF-1, and osteopontin, indicating a decrease in CNS inflammation. Neuroprotective biomarkers, such as VEGF-A, HGF, NCAM1, and LIF, also showed consistent increases, suggesting that MSC-NTF cells might help support neuronal health and function in PMS. However, changes in neurodegenerative biomarkers, such as neurofilament light chain (NfL), were inconsistent, indicating the need for additional research to understand MSC-NTF’s impact on neuronal damage markers.
Insights and Future Directions Of MSC-NTF Therapy for PMS
This open-label, single-arm Phase II study demonstrated that MSC-NTF cells could be safely administered in participants with stable, non-relapsing PMS. Although two participants experienced arachnoiditis following intrathecal treatment, the majority tolerated the therapy well. Functional outcomes showed encouraging trends, suggesting possible benefits of MSC-NTF therapy in improving physical and cognitive function in PMS patients.
The study also highlighted several limitations, including the lack of a placebo-controlled group, which may introduce bias in interpreting efficacy results, and limitations in biomarker analysis due to sample timing. Additionally, inconsistent changes in neurodegenerative biomarkers and the small sample size warrant further investigation.
In summary, this Phase II trial provides preliminary evidence supporting the safety and potential therapeutic benefits of MSC-NTF cell therapy in PMS. While these initial findings are promising, larger placebo-controlled studies are needed to confirm efficacy and further elucidate the role of MSC-NTF cells in modulating CNS inflammation and promoting neuroprotection in PMS.
Source: Cohen JA, Lublin FD, Lock C, et al. Evaluation of neurotrophic factor secreting mesenchymal stem cells in progressive multiple sclerosis. Multiple Sclerosis Journal. 2023;29(1):92-106. doi:10.1177/13524585221122156
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