Multiple sclerosis (MS) is a debilitating autoimmune disease of the brain and spinal cord. The disease can affect everyone differently, but depending on the progression and severity of the disease, patients may have vision problems, numbness and tingling, muscle weakness, coordination problems, pain, fatigue, and bladder dysfunction, among others. Risk factors associated with MS include family history, low vitamin D levels, obesity, and smoking. Unfortunately, there is no cure for MS, but it can be managed with medications and physical therapy that mediate symptoms and slow disease progression.
Multiple sclerosis deteriorates the outer layer of nerve cells, known as myelin sheaths. The protective sheath layer helps move and coordinate messages from the body to the brain and vice versa. Once it starts to deteriorate, signals to the brain become slower, and signals to react to outside stimuli become delayed. As the disease progresses, patients become extremely inactive and find it hard to complete daily tasks. Medications include immunosuppressants, but they weaken the immune system. Scientists are currently studying new ways to improve MS treatment and reduce symptoms.
A recent article in the Journal of Clinical Investigation by Dr. Eva Martinez-Caceres and others demonstrates how targeted immune cell therapy can slow down MS and prevent the immune system from attacking the myelin sheath. Martinez-Caceres is a scientific Group Leader for the Immunopathology Research Group at the Germans Trias I Pujol Research Institute and focuses on different aspects of immunopathology, including autoimmune diseases, cellular immunology, and immune-mediated therapies.
Martinez-Caceres and her team targeted tolerogenic dendritic cells (tolDCs) to restore immune function and avoid autoimmunity. Tolerogenic dendritic cells are specialized immune cells that can regulate immune tolerance and prevent cells from attacking the body. Since MS is the dysregulation of the immune system, these cells do not function properly. In the report, researchers study tolDCs in healthy and MS patients who have not received treatment—the clinical trial aimed to assess the effectiveness of tolDCs, which were treated with vitamin D3. The VitD3-tolDCs were meant to restore the immune system and prevent cells from attacking the myelin sheath. Targeted cell therapy is unique because it takes the patient’s immune cells and modifies them to correct immune system imbalance.
Further investigation led the researchers to conclude that MS patient immune cells have pro-inflammatory characteristics even after treatment with vitamin D3. Although VitD3-tolDCs were demonstrated to reduce myelin deterioration, the inflammatory signature from MS patients was less effective compared to healthy individuals.
With various scientific techniques, Martinez-Caceres and others identified a critical pathway associated with an altered immune response, the Aryl Hydrocarbon Receptor (AhR) pathway. Through AhR-targeted therapy, researchers could fully restore function in VitD3-tolDCs from MS patients. Interestingly, an approved MS drug, known as Dimethyl Fumarate, works similarly and allows full efficacy that is less toxic. Additionally, VitD3-tolDCs combined with Dimethyl Fumarate elicit a more robust response in patients compared to either treatment as a single agent. This work done in animal models demonstrates the translational potential to the clinic. Overall, combination therapy to redirect tolDCs advances the field and provides more information to develop potent therapies against autoimmune disorders, particularly MS.
Article, Journal of Clinical Investigation, Eva Martinez-Caceres, Germans Trias i Pujol Research Institute