2025-05-30
Progressive MS: could the placenta pave the way?
Neurology
#MultipleSclerosis #MS #CellTherapy
#Immunomodulation #Cytokines #Neuroinflammation
Multiple sclerosis (MS) is a chronic, progressive autoimmune disease of the central nervous system, primarily affecting young adults. It is characterized by persistent inflammation, demyelination of nerve fibers, and progressive axonal degeneration, which lead to a wide range of neurological symptoms. While relapsing forms of MS benefit from effective immunomodulatory treatments, the secondary progressive form (SPMS), which appears after several years, remains challenging to manage.
In SPMS, patients experience a continuous worsening of neurological disability without evident inflammatory relapses, limiting the effectiveness of standard treatments. Current approaches mainly target immune response modulation, but no strategy has yet succeeded in restoring lost neuronal function or halting disease progression. Resistance to existing therapies, lack of clinical response, and the absence of regenerative treatments are major challenges for this patient population.
In this constrained therapeutic context, placenta-derived mesenchymal stem cells (PLMSCs) are generating growing interest. Current data suggest they can modulate immunity, reduce inflammation, and promote neuroprotection and possibly repair. These cells are low in immunogenicity and have demonstrated an excellent safety profile, making them a promising and innovative option for progressive forms of MS.
This study was launched to assess the tolerance, safety, and exploratory clinical, cognitive, immunological, and radiological effects following a single intravenous injection of PLMSCs. This protocol is a key step in evaluating the feasibility of a cell-based approach in this advanced and treatment-resistant form of MS.
In this study, five patients with SPMS were selected and followed for six months, with a comprehensive assessment protocol that included:
No serious adverse events were reported, except for transient headaches in two patients within hours of injection. Neurologically, clinical improvement was observed, with a significant reduction in EDSS scores (P < 0.0001).
Cognitively, substantial gains were noted in several neuropsychological subtests, indicating improvements in attention, executive function, and memory. DTI imaging revealed a significant reduction in radial diffusivity, suggesting decreased cerebral oxidative stress. Concurrently, functional MRI showed an increase in post-injection functional brain connectivity.
From an immunological standpoint, a significant decrease in B-cell CD19/CD20 expression was observed, accompanied by a marked increase in the anti-inflammatory cytokine IL-10 and a notable reduction in pro-inflammatory cytokines IL-6, TNFα, and IL-17—indicating a shift toward a more regulated and less inflammatory immune profile.
Secondary progressive multiple sclerosis is an advanced stage of the disease marked by irreversible accumulation of disability, for which therapeutic options remain limited. The main challenge lies in the ineffectiveness of conventional treatments, the lack of strategies for neuronal repair, and the silent, uncontrolled progression of inflammation and axonal degeneration.
In this context, the study aimed to evaluate the safety, tolerability, and exploratory clinical, cognitive, radiological, and immunological effects of a single intravenous injection of placenta-derived mesenchymal stem cells in patients with SPMS. The results suggest that PLMSCs are well-tolerated, with no serious adverse effects, and may positively influence neurological, cognitive, and immune functions. Advanced MRI data and biomarker evolution hint at a potential neuroprotective—and possibly regenerative—effect of PLMSCs in this progressive form.
Despite these encouraging findings, the study has several major limitations, justifying further clinical trials. Future trials involving larger cohorts, long-term follow-up, control groups, and evaluation of multiple-injection protocols will be essential to confirm the true clinical efficacy of PLMSCs and refine their future integration into the management of progressive MS.
Multiple sclerosis (MS) is a chronic, progressive autoimmune disease of the central nervous system, primarily affecting young adults. It is characterized by persistent inflammation, demyelination of nerve fibers, and progressive axonal degeneration, which lead to a wide range of neurological symptoms. While relapsing forms of MS benefit from effective immunomodulatory treatments, the secondary progressive form (SPMS), which appears after several years, remains challenging to manage.
In SPMS, patients experience a continuous worsening of neurological disability without evident inflammatory relapses, limiting the effectiveness of standard treatments. Current approaches mainly target immune response modulation, but no strategy has yet succeeded in restoring lost neuronal function or halting disease progression. Resistance to existing therapies, lack of clinical response, and the absence of regenerative treatments are major challenges for this patient population.
In this constrained therapeutic context, placenta-derived mesenchymal stem cells (PLMSCs) are generating growing interest. Current data suggest they can modulate immunity, reduce inflammation, and promote neuroprotection and possibly repair. These cells are low in immunogenicity and have demonstrated an excellent safety profile, making them a promising and innovative option for progressive forms of MS.
This study was launched to assess the tolerance, safety, and exploratory clinical, cognitive, immunological, and radiological effects following a single intravenous injection of PLMSCs. This protocol is a key step in evaluating the feasibility of a cell-based approach in this advanced and treatment-resistant form of MS.
Cells to awaken neurons?
In this study, five patients with SPMS were selected and followed for six months, with a comprehensive assessment protocol that included:
- Clinical (EDSS), cognitive (MACFIMS battery), and advanced brain imaging (DTI, fMRI) evaluations;
- Analysis of immunological markers (IL-10, TNFα, IL-6, IL-17) and B-cell subpopulations (CD19/CD20).
No serious adverse events were reported, except for transient headaches in two patients within hours of injection. Neurologically, clinical improvement was observed, with a significant reduction in EDSS scores (P < 0.0001).
Cognitively, substantial gains were noted in several neuropsychological subtests, indicating improvements in attention, executive function, and memory. DTI imaging revealed a significant reduction in radial diffusivity, suggesting decreased cerebral oxidative stress. Concurrently, functional MRI showed an increase in post-injection functional brain connectivity.
From an immunological standpoint, a significant decrease in B-cell CD19/CD20 expression was observed, accompanied by a marked increase in the anti-inflammatory cytokine IL-10 and a notable reduction in pro-inflammatory cytokines IL-6, TNFα, and IL-17—indicating a shift toward a more regulated and less inflammatory immune profile.
A cellular hope on the horizon
Secondary progressive multiple sclerosis is an advanced stage of the disease marked by irreversible accumulation of disability, for which therapeutic options remain limited. The main challenge lies in the ineffectiveness of conventional treatments, the lack of strategies for neuronal repair, and the silent, uncontrolled progression of inflammation and axonal degeneration.
In this context, the study aimed to evaluate the safety, tolerability, and exploratory clinical, cognitive, radiological, and immunological effects of a single intravenous injection of placenta-derived mesenchymal stem cells in patients with SPMS. The results suggest that PLMSCs are well-tolerated, with no serious adverse effects, and may positively influence neurological, cognitive, and immune functions. Advanced MRI data and biomarker evolution hint at a potential neuroprotective—and possibly regenerative—effect of PLMSCs in this progressive form.
Despite these encouraging findings, the study has several major limitations, justifying further clinical trials. Future trials involving larger cohorts, long-term follow-up, control groups, and evaluation of multiple-injection protocols will be essential to confirm the true clinical efficacy of PLMSCs and refine their future integration into the management of progressive MS.
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Progressive MS: could the placenta pave the way?
#MultipleSclerosis #MS #CellTherapy #Immunomodulation #Cytokines #Neuro...
