July 7, 2023 : In recent years, the remarkable success of chimeric antigen receptor T cell (CAR T) therapy in sending difficult-to-treat blood cancers into remission has garnered significant attention. A small clinical trial suggests this innovative therapy could be adapted to treat myasthenia gravis, a rare autoimmune disease. The trial, which demonstrated a favorable safety profile and the possibility of long-lasting symptom reduction, has paved the way for a larger-scale randomized control study set to conclude in December of this year.
Myasthenia gravis is a lifelong autoimmune disease that affects 20 out of every 100,000 Americans. In this condition, the immune system erroneously attacks the body’s tissues, particularly damaging communication between neurons and muscles. This disruption prevents proper contraction of the skeletal muscles responsible for controlling the eyes, face, arms, legs, and more.
CAR T therapy is a cutting-edge cell-based treatment that genetically modifies a patient’s immune cells to fight cancer. However, traditional CAR T therapy carries unfavorable risks for individuals with myasthenia gravis. The therapy’s inability to be controlled once infused often leads to an overstimulated immune system, potentially exacerbating complications in patients with an already overactive immune system and neurological symptoms.
In a recent study, researchers explored an alternative CAR T therapy called Descartes-08, originally developed for multiple myeloma but later repurposed for myasthenia gravis. The therapy relies on synthetic mRNA, which naturally degrades in T cells after a week, allowing control over the therapy’s effects. This mRNA-based CAR T therapy can potentially mitigate the risks associated with traditional CAR T therapy, including immune system overload and the need for lymphodepletion.
The study involved 14 participants with generalized myasthenia gravis who were already taking immunosuppression drugs. The therapy’s safety and ideal dosing schedule were assessed, with one infusion per week for six weeks determined to be the most effective. Participants in this group experienced significant and sustained reductions in disease severity, with some showing minimal symptoms even months after treatment.
Encouragingly, the CAR T therapy demonstrated a favorable safety profile without any dose-limiting toxicities or treatment-related serious adverse events. Notably, none of the patients experienced cytokine release syndrome or neurotoxicity, the common adverse effects of traditional CAR T therapy. The adverse events were resolved within 24 hours of the infusion.
These promising results indicate that with necessary adjustments, CAR T therapy could offer a safe and lasting reduction in symptoms for individuals with myasthenia gravis. The ability to target pathogenic plasma cells is particularly innovative in myasthenia gravis treatment. The ongoing larger randomized control trial will provide further insight into the potential of mRNA-based CAR T therapy for rare autoimmune diseases like myasthenia gravis.