Multiple sclerosis (MS) is an autoimmune disease where the immune system attacks the protective myelin sheath on nerve fibers. This damage disrupts brain-to-body communication, causing neurological symptoms. Researchers are now investigating CAR T-cell therapy, a treatment traditionally used for cancer, as a new way to address the autoimmune attack in MS.
The Foundation of CAR T–Cell Therapy
CAR T-cell therapy is an immunotherapy using a patient’s own T-cells. The process begins by collecting T-cells from blood via leukapheresis. In a lab, the cells are genetically modified with a disarmed virus to produce surface structures called Chimeric Antigen Receptors (CARs).
These receptors act as a guidance system, enabling the modified T-cells to recognize and bind to specific proteins (antigens) on target cells. After engineering, these new CAR T-cells are multiplied in a lab to ensure a sufficient quantity for treatment.
Finally, the CAR T-cells are infused back into the patient. Before this, a short course of chemotherapy called lymphodepletion reduces existing T-cells, helping the new cells establish themselves. In cancer treatment, these cells are programmed to destroy malignant cells and have proven effective for certain blood cancers.
Targeting Multiple Sclerosis at its Source
For multiple sclerosis, CAR T-cell therapy’s target shifts from cancer cells to the immune cells driving the disease. Research identifies B-cells as a primary contributor, as they produce antibodies that attack the myelin sheath, leading to the nerve damage seen in MS.
CAR T-cells for MS are engineered to recognize a protein on B-cells, commonly the CD19 antigen. Targeting CD19 allows the therapy to selectively eliminate the B-cells causing the autoimmune response. This approach provides a precise “reset” by removing the problem cells, which should halt the production of harmful antibodies and stop the attack on the central nervous system.
This targeted depletion has an advantage over broader immunosuppression therapies. Some current treatments use antibodies that struggle to cross the blood-brain barrier, where much MS damage occurs. As living cells, CAR T-cells may be better equipped to reach these protected areas, aiming for a deep reduction of problematic B-cells and potential long-term remission without continuous medication.
Emerging Clinical Evidence
Early-phase clinical trials are now testing CAR T-cell therapy for multiple sclerosis. These initial, small studies have yielded encouraging results, with some patients with aggressive forms of MS experiencing significant improvements after treatment.
Some trial participants have achieved drug-free remission, with MS symptoms subsiding without ongoing medication. These clinical improvements are supported by magnetic resonance imaging (MRI) scans, which have shown an absence of new inflammatory brain lesions in treated patients.
The number of patients treated is limited, and the long-term effects are still being studied. Phase 1 and 2 studies are underway to evaluate the safety, dosage, and efficacy across different MS forms, including relapsing and progressive types. Results from these trials will determine if this therapy can become a widely available treatment.
Navigating the Risks and Complications
CAR T-cell therapy has notable risks. A common and serious side effect is Cytokine Release Syndrome (CRS), which occurs when CAR T-cells multiply and attack their targets. This leads to a massive release of inflammatory molecules called cytokines, causing systemic inflammation with symptoms ranging from fever to life-threatening organ issues.
Another concern is Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which involves neurological symptoms like confusion, language difficulty, or seizures. ICANS is believed to result from inflammation and a breakdown of the blood-brain barrier, allowing inflammatory cells into the central nervous system.
Experienced medical teams have protocols to manage these side effects. Both CRS and ICANS are reversible with prompt intervention, including medications to counteract the inflammation. Because of these potential complications, the therapy is only administered in specialized medical centers.