A new study led by researchers at the UNC School of Medicine and Cartesian Therapeutics, found that immunotherapy can help people with generalized myasthenia gravis, a disease where the body accidentally attacks the cells that help your nerves and muscles work together, causing variable muscle weakness and fatigue.
"The results of this trial indicate that a valuable new treatment opportunity in gMG-a brief course of treatment leading to at least a year-long benefit-may be achievable," said James Howard Jr., MD, who is senior author on the paper and expert on myasthenia gravis at the UNC Department of Neurology.
The new treatment helps close a significant gap in care for patients with generalized myasthenia gravis. Existing medications for the condition can increase the risk of urinary tract infections and upper respiratory infections in patients-and often take a long time for patients to see results. Results from the clinical trial were published in Nature Medicine.
James Howard, MD
Chimeric antigen receptor (CAR) T-cell therapy is being used to treat complex cancers and autoimmune conditions, like lupus. A kind of immunotherapy, CAR T-cell therapy reprograms your body's own immune cells to better fight off disease, oftentimes resulting in drug-free remissions and an 'immune reset.'
The blinded multicenter, phase 2b trial took place at UNC and other universities in Canada and Türkiye. In this study, researchers tested a type of CAR T‑cell therapy called Descartes‑08.
Descartes-08 is an mRNA-based CAR T-cell therapy that uses immune cells harvested from the patient's own blood to reduce the body's production of harmful and irregular antibodies. The mRNA-based therapy, as opposed to DNA-based CAR T-cell therapy, does not modify the patient's genetic material and so far has not been associated with serious side effects.
Twenty-six adult participants with various subtypes of generalized myasthenia gravis (determined by antibody presence) were enrolled in the trial. Of the total number of participants, nineteen (73.1%) were AChR autoantibody-positive, one (3.8%) was LRP4 autoantibody-positive, and six (23.1%) were triple seronegative.
Fifteen participants received six once-weekly doses of Descartes-08 in an outpatient setting. Eleven participants received a placebo. Over the course of twelve months, researchers used a combination of physician and participant reported outcomes to assess the efficacy of treatment.
In the phase 2b trial, about 57% of participants achieved minimal symptom expression-essentially no disease-by month six. Even more impressively, participants continued to see maintained results through month twelve.
Following the encouraging trial, Nature Medicine named the Descartes-08 trial as one of eleven "clinical trials to watch in 2026," as they have great potential to shape the field of precision medicine and global health. Howard described how the therapy could be the next outpatient, first-line treatment for generalized myasthenia gravis and other autoimmune diseases.
"It is a real next step in long-lasting, precise immunotherapy," said Howard. "And the implications go beyond myasthenia gravis, because this mRNA CAR T cell approach could eventually extend to other autoimmune diseases, such as multiple sclerosis, lupus or rheumatoid arthritis."
Researchers are also running a larger clinical trial to confirm their results in patients with anti-AChR antibody-positive disease, the most common subtype of generalized myasthenia gravis.
