This is about neural stem cells in progressive MS. Be careful, there is a risk of confusion: I had already taken a stance on stem cell therapy in the DocBlog (see DocBlog from 25.10.2019) – however on the transplantation of so-called autologous hematopoietic stem cells. Even then, I emphasized that when discussing stem cells and stem cell transplantation, one always has to define exactly what is meant.
Autologous hematopoietic stem cells
The transplantation of autologous hematopoietic stem cells (AHSCT), which has been well studied in clinical trials, is a method for reconstituting the immune system – thus a maximum anti-inflammatory treatment strategy that could be especially suitable for young and highly active MS patients and is now being advanced in Germany by the initiative of the Competence Network MS (KKNMS) (German Task Force for AHSCT in MS established). However, MS experts largely agree that AHSCT probably has no lasting effect in the progressive phase of the disease.
However, patients with progressive MS and MS-related disabilities in particular hope for help through new therapies. The term “stem cell therapy” raises the hope of being able to replace damaged nerve cells and restore bodily functions. However, autologous hematopoietic stem cells are not suitable for this purpose, instead, the hope lies in so-called neural or neuronal stem cells.
Neural stem cells
Neural stem/ precursor cells (neuronal precursor cells – NPC) are proliferative, self-renewing and multipotent cells that are capable of differentiating into astrocytes, oligodendrocytes and neurons. In theory, it is hoped that these cells will migrate into specific biological niches or damaged areas and promote the function of the nerve tissue through structural repair. However, such an approach always raises the concern that the proliferating stem cells can no longer be controlled and in the worst case lead to the formation of rapidly growing tumors. Therefore, cautious scientific progress is necessary in the field of neural stem cell transplantation and its application in humans is fraught with many question marks.
Therefore, it is significant that science has made some progress in this exciting field. In early January, Italian researchers published a phase I study on the application of neural stem cells in patients with progressive MS in the renowned scientific journal Nature Medicine (Genchi A et al. Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study. Nat Med. 2023 Jan;29(1):75-85). I would like to briefly introduce and classify this study, which was also intensively discussed on social networks when it was published.
Safety study for NPC: Phase 1
The study is an open clinical phase I study on 12 patients with progressive MS (PMS – with indication of disease progression, EDSS ≥6.5, age 18-55 years, disease duration 2-20 years, without alternative approved therapy). The patients were enrolled in four treatment cohorts (TC) and received intrathecal (through lumbar puncture) human fetal neural stem cells (hfNPC) in escalating treatment doses (TC-A: 0.7 × 106; TC-B: 1.4 × 106; TC-C: 2.8 × 106; TC-D: 5.7 x 106 ± 10 % viable cells per kilogram of body weight).
The primary objective of the study was to evaluate the feasibility, safety and tolerability of intrathecal administration of hfNPCs in patients with PMS. The safety of hfNPC administration was evaluated with 22 follow-up examinations over a period of 96 weeks, with survival and adverse events (AEs) being evaluated. In addition, hypothesis-generating data on potential treatment effects of hfNPCs were to be obtained.
The primary safety endpoint was achieved. No serious side effects associated with hfNPC were found in the 2-year follow-up. Exploratory analyses showed lower brain atrophy in patients who received the highest dose of hfNPC. Furthermore, increased levels of anti-inflammatory and neuroprotective factors were found in the cerebrospinal fluid.
Next step: Testing the efficacy of NPC in MS
The authors of the current Italian study have thus achieved an important step by investigating the safety and feasibility of intrathecal administration of hfNPC. However, no conclusions can be drawn about the effectiveness of this therapy with the help of the study. Some interesting efficacy endpoints are discussed, but their interpretation should be treated with great caution.
In addition, it must be taken into account that the very small, non-controlled study does not yet allow any definitive statements about safety. Therefore, larger studies should be awaited before determining whether the concept of hfNPC administration is viable for the future. In any case, at this point in time, false hopes for this form of therapy should not be raised in patients with progressive MS. Also, the new Italian study should not be mixed with the findings on autologous hematopoietic stem cell transplantation – it is a completely different approach.
