Cell therapy in multiple sclerosis: An overview.

Area of Science:

• Neuroimmunology
• Cellular Therapy
• Regenerative Medicine

Background:

• Multiple sclerosis (MS) therapy advances leave unmet needs, especially for disability progression and progressive/aggressive forms.
• Current high-efficacy therapies control inflammation but have limited impact on neurodegeneration.
• Progressive MS (PMS) has scarce therapeutic options.

Purpose of the Study:

• To review the current state and future potential of cell-based therapies for multiple sclerosis.
• To evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (AHSCT), CAR T-cells, and mesenchymal stromal cells (MSCs) in MS treatment.
• To highlight the need for further research and optimized strategies for cell-based therapies in MS.

Main Methods:

• Review of randomized trials and observational cohorts for AHSCT in aggressive MS.
• Analysis of early clinical reports on CAR T-cell therapies (CD19 and BCMA) in progressive MS.
• Examination of clinical studies on Mesenchymal Stromal Cells (MSCs) for MS, including intrathecal administration.

Main Results:

• AHSCT demonstrates sustained suppression of inflammatory activity and high rates of no evidence of disease activity in aggressive MS.
• CAR T-cell therapies show CNS penetration, manageable toxicity, and preliminary clinical improvement signals in progressive MS.
• MSC studies suggest potential benefits, particularly with intrathecal delivery, but efficacy is inconsistent due to study heterogeneity.

Conclusions:

• Cell-based therapies, including AHSCT, CAR T-cells, and MSCs, hold significant promise for addressing unmet needs in multiple sclerosis.
• Further robust randomized trials, optimized delivery methods, and precise patient selection are crucial for defining the therapeutic role of these cell-based interventions.
• AHSCT is recommended for highly active MS refractory to DMTs; its role in non-inflammatory progressive MS is debated.