A team of researchers has found that combining tolerogenic dendritic cells with dimethyl fumarate improves the efficacy of multiple sclerosis treatment, offering a promising new approach for managing the disease.
Multiple sclerosis: a promising new therapeutic approach is on the way
Multiple sclerosis (MS) is a chronic condition in which the immune system mistakenly attacks the myelin sheath, the protective covering around nerve cells, causing nerve damage and increased disability.
Existing treatments such as immunosuppressants mitigate these attacks but compromise the immune system, making patients more susceptible to infections and cancer. Researchers are studying a new, more targeted approach that involves using a type of immune cell called tolerogenic dendritic cells (tolDCs), derived from patients themselves, to target the disease more precisely.
TolDCs can restore immune balance without affecting the body’s natural defenses. However, since a hallmark of multiple sclerosis is immune system dysfunction, the effectiveness of these cells for autotransplantation may be compromised. Therefore, it is essential to better understand how disease affects the starting material for this cell therapy before it can be applied.
In this study, published in the prestigious journal Journal of Clinical Investigation researchers examined 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 healthy individuals.
The clinical trials (NCT02618902 and NCT02903537), conducted in Spain by Dr. Cristina Ramo-Tello and Dr. Eva Martínez Cáceres (Germans Trias i Pujol Research Institute), are designed to evaluate the effectiveness of VitD3-tolDC, which they are loaded with myelin antigens to help “teach” the immune system to stop attacking the nervous system. This approach is revolutionary as it uses the patient’s own immune cells, modified to induce immune tolerance, in an attempt to treat the autoimmune nature of multiple sclerosis.
The study, conducted by Dr. Eva Martinez-Cáceres and Dr. Esteban Ballestar (Josep Carreras Institute), with Federico Fondelli as first author, discovered that the immune cells of MS patients (monocytes, precursors of tolDCs) have a persistent “pro-inflammatory” signature, even after being transformed into VitD3-tolDC, the actual therapeutic cell type. This signature makes these cells less effective than those derived from healthy individuals, losing some of its potential benefits.
Using cutting-edge research methodologies, researchers have identified a pathway, known as the Aryl Hydrocarbon Receptor (AhR), that is linked to this altered immune response. Using an AhR-modulating drug, the team was able to restore the normal function of VitD3-tolDCs from multiple sclerosis patients, in vitro. Interestingly, Dimethyl Fumarate, an already approved MS drug, mimicked the effect of AhR modulation and restored full cell efficacy, with a safer toxic profile.
Finally, studies in multiple sclerosis animal models have shown that a combination of VitD3-tolDC and Dimethyl Fumarate led to better outcomes than using either treatment alone. This combination therapy significantly reduced symptoms in mice, suggesting improved potential for treating human patients.
These findings could lead to a new, more powerful treatment option for multiple sclerosis, offering hope to the millions of patients around the world who suffer from this debilitating disease.
This study represents a significant step forward in the use of personalized cell therapies for autoimmune diseases, potentially revolutionizing the way autoimmune disease is treated. multiple sclerosis.
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