Stem Cell Therapy for Multiple Sclerosis: Biomarkers Validate Mechanism in Progressive Patients

Evaluating Stem Cell Therapy for Multiple Sclerosis Efficacy

Repeated intrathecal injections of autologous Mesenchymal stem cell-neural progenitors (MSC-NP) induce measurable proteomic shifts in cerebrospinal fluid (CSF). This confirms biological activity in the central nervous system for patients with non-active progressive MS. Progressive Multiple Sclerosis (MS) remains a stubborn clinical challenge. Treatments often fail to halt neurodegeneration or repair existing damage. A new analysis examines the biological impact of stem cell therapy for multiple sclerosis using bone marrow-derived progenitors. By studying 93 patients across two cohorts, researchers identified a specific protein signature that confirms the treatment engages the central nervous system.

These results were observed under controlled laboratory conditions, so real-world performance may differ.

The Problem: Silent Progression

Non-active progressive MS degrades neural function slowly. Standard drugs struggle to penetrate the blood-brain barrier effectively. Furthermore, clinicians lack precise tools to determine if a cell-based therapy is engaging its target. Without measurable biological signals, dosing becomes a guessing game. Physicians observe clinical outcomes, which can take years to manifest. They need immediate data to verify that the therapeutic agents are active and effective.

The Solution: Intrathecal Analysis

Researchers administered autologous MSC-NPs directly into the spinal canal. This route bypasses the blood-brain barrier. The team analysed CSF from subjects in a Phase 2 trial (n=50) and an expanded access trial (n=43). They screened for proteomic changes distinct from serum levels. This isolation confirms the changes occur within the central nervous system, not the periphery. The study sought to validate whether the cells were simply present or if they were modifying the neural environment.

The Mechanism: Four Specific Signals

The analysis isolated four proteins that shifted significantly post-treatment. These serve as a fingerprint for the therapy's activity:

• CCL2 (C-C motif chemokine ligand-2): A protein involved in immune regulation and cell recruitment.
• MMP9 (Matrix metalloproteinase-9): An enzyme linked to tissue remodelling and cell migration.
• SCF (Stem cell factor): A cytokine essential for haematopoiesis and cell survival.
• CHIT1 (Chitotriosidase-1): A marker indicating macrophage activation.

Notably, standard markers of neurodegeneration—neurofilament light (NfL) and glial acidic fibrillary protein (GFAP)—did not change following treatment. Instead, NfL and GFAP tracked with age and disability scores (EDSS). This suggests the therapy triggers specific immunomodulatory and trophic pathways rather than immediately reversing structural damage markers. The treatment modulates the environment; it does not instantly erase the scars of the disease.

The Impact: Towards Precision Dosing

These findings move the field beyond subjective clinical observations. If CCL2 or SCF levels correlate with clinical benefit, they become targets. Physicians could theoretically adjust the frequency of injections based on these fluid biomarkers. It shifts the protocol from fixed schedules to biologically responsive treatment. While the study confirms safety, it suggests that measuring these specific proteins is necessary to optimise future trials. We now have a biological ruler to measure the efficacy of these cells.