Multiple sclerosis (MS) is a chronic disease where the immune system mistakenly attacks the protective layer around nerve cells, leading to nerve damage and increasing disability. Current treatments, such as immunosuppressants, help reduce these attacks but weaken the overall immune system, making patients more susceptible to infections and cancer. Scientists are now exploring a more targeted therapy using special immune cells called tolerogenic dendritic cells (tolDCs) from the patients themselves.
TolDCs can restore immune balance without compromising natural defenses. However, the dysfunction of the immune system in MS patients may affect the effectiveness of these cells for auto transplantation. Therefore, it is crucial to understand how the disease impacts the starting material for this cellular therapy before its application.
A recent study published in the Journal of Clinical Investigation focused on CD14+ monocytes, mature dendritic cells (mDCs), and Vitamin D3-treated tolerogenic dendritic cells (VitD3-tolDCs) from MS patients who had not yet received treatment, as well as from healthy individuals. The clinical trials, led by Dr. Cristina Ramo-Tello and Dr. Eva Martínez Cáceres of the Germans Trias i Pujol Research Institute, aimed to evaluate the efficacy of VitD3-tolDCs loaded with myelin antigens to teach the immune system to stop attacking the nervous system. This approach uses a patient’s own immune cells modified to induce immune tolerance, offering a groundbreaking strategy to address the autoimmune nature of MS.
The study, led by Dr. Eva Martinez-Cáceres and Dr. Esteban Ballestar of the Josep Carreras Institute, identified a persistent “pro-inflammatory” signature in immune cells from MS patients, even after their transformation into VitD3-tolDCs. This signature compromised the efficacy of these cells, missing out on their full potential benefits. Through advanced research techniques, the researchers discovered the Aryl Hydrocarbon Receptor (AhR) pathway linked to this altered immune response. By using an AhR-modulating drug, the team successfully restored the normal function of VitD3-tolDCs from MS patients in vitro. Notably, Dimethyl Fumarate, an approved MS drug, mimicked the effects of AhR modulation, enhancing the cells’ efficacy with a safer toxic profile.
Furthermore, studies in MS animal models demonstrated that a combination of VitD3-tolDCs and Dimethyl Fumarate produced superior results compared to individual treatments. This combination therapy significantly alleviated symptoms in mice, hinting at enhanced potential for treating human patients.
These findings pave the way for a more potent treatment option for MS, offering hope to millions of patients worldwide battling this debilitating disease. This research signifies a significant advancement in personalized cell therapies for autoimmune diseases, potentially transforming the landscape of multiple sclerosis treatment.
Funded by public funds from the Spanish Government (ISCIII, FEDER, and MICINN) and the EU Horizon program (INsTRuCT and RESTORE projects), this research marks a significant milestone in the quest for innovative solutions in MS treatment. The integration of VitD3-tolDCs and Dimethyl Fumarate could usher in a new era in managing multiple sclerosis, heralding a brighter future for patients grappling with this challenging condition.
