A new study suggests a combination of specially treated immune cells and an already approved disease-modifying treatment may offer better results in treating multiple sclerosis than using either on its own. Researchers said the findings represent a significant step forward in the use of personalized cell therapies, potentially revolutionizing how MS is treated.

MS is a chronic disease where the immune system mistakenly attacks the protective layer around nerve cells known as the myelin sheath. This leads to nerve damage and worsening disability. Current treatments, such as immunosuppressants, help reduce these harmful attacks but also weaken the overall immune system, leaving patients vulnerable to infections and cancer. Scientists are now exploring a more targeted therapy using special immune cells, called tolerogenic dendritic cells, from the same patients.

Tolerogenic dendritic cells can restore immune balance without affecting the body’s natural defenses. However, because a hallmark of MS is precisely the dysfunction of the immune system, the effectiveness of these cells for auto transplantation might be compromised. Therefore, it is essential to better understand how the disease affects the starting material for this cellular therapy before it can be applied.

In this study, researchers at the Josep Carreras Leukaemia Research Institute, in Barcelona, Spain, examined CD14+ monocytes, mature dendritic cells, and vitamin D3-treated tolerogenic dendritic cells from MS patients who had not yet received treatment, as well as from healthy individuals. The clinical trials were designed to assess the effectiveness of vitamin D3-treated tolerogenic dendritic cells, which were loaded with myelin antigens to help "teach" the immune system to stop attacking the nervous system. This uses a patient’s own immune cells which are modified to induce immune tolerance to try and treat the autoimmune nature of MS.

The study found the immune cells from MS patients (monocytes, precursors of tolerogenic dendritic cells) have a persistent “proinflammatory” signature, even after being transformed into Vitamin D3-treated tolerogenic dendritic cells, the actual therapeutic cell type. This signature makes these cells less effective compared to those derived from healthy individuals, missing part of its potential benefits.

The researchers identified a pathway, known as the Aryl hydrocarbon receptor, which is linked to this altered immune response. By using an AhR-modulating drug, the team was able to restore the normal function of Vitamin D3-treated tolerogenic dendritic cells from MS patients, in vitro. Interestingly, dimethyl fumarate, an already approved MS drug, was found to mimic the effect of AhR modulation and restore the cells to full efficacy, with a safer toxic profile.

Finally, studies in MS animal models showed that a combination of vitamin D3-treated tolerogenic dendritic cells and dimethyl fumarate led to better results than using either treatment on its own. This combination therapy significantly reduced symptoms in mice, suggesting enhanced potential for treating human patients.

These results could lead to a new, more potent treatment option for MS, offering hope to the millions of patients worldwide who suffer from this debilitating disease. Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, researchers said this study represents a significant step forward in the use of personalized cell therapies for autoimmune diseases, potentially revolutionizing how MS is treated.

The study was published in the Journal of Clinical Investigation.