UCI tests cell therapy for myasthenia gravis, the first use of CAR T-cells to treat an autoimmune disease

November 08, 2022
Dr. Tahseen Mozaffar is a board-certified UCI Health neurologist who directs the UCI Health ALS & Neuromuscular Center..
The Descartes-08 CAR T-cell therapy now in clinical trials may offer patients with generalized myasthenia gravis a potential long-term treatment, said Dr. Tahseen Mozaffar, director of the UCI Health ALS & Neuromuscular Center.  

Irvine, Calif. — UCI Health and the UCI Alpha Clinic are conducting a clinical trial of an investigational cell therapy in patients with generalized myasthenia gravis, a rare autoimmune disorder.

The therapy, called Descartes-08, is an mRNA-modified, autologous CAR T-cell product designed to attack B-cell maturation antigen. It is the first clinical trial using CAR T-cell therapy to treat an autoimmune disease. 

“There is no known cure for generalized myasthenia gravis,” said Tahseen Mozaffar, MD, a UCI Health neurologist and the trial’s principal investigator at UCI. “While other treatments offer some short-term relief, determining whether mRNA-modified cell therapies can be safely and cost-effectively used to treat autoimmune diseases like generalized myasthenia gravis offers patients the possibility of a long-term treatment.”

CAR T-cell therapies have been a huge success in treating some cancers, but their use of integrated DNA carries a long term risk for severe complications, Mozaffar said. RNA-based CAR T-cell therapies minimize that risk and offer the potential of significant long-term benefit with minimal side effects. Descartes-08, unlike other available therapies, specifically targets the production of disease-causing antibodies by addressing the role of plasma cells, which are the antibody-producing cells that cause generalized myasthenia gravis.

According to the National Institute for Neurological Disorders and Stroke, myasthenia gravis is a chronic, autoimmune neuromuscular disease that causes weakness in the skeletal muscles, which worsens after periods of activity and improves after periods of rest. Skeletal muscles are responsible for functions involving breathing and moving parts of the body, including the arms and legs. The disorder — which affects almost 200,000 patients in the United States, Europe and Japan — causes a variety of symptoms ranging from drooping eyelids and double vision to debilitating muscle weakness and respiratory failure.

In 2021, clinical trial sponsor Cartesian Therapeutics released results from the first cohort of the ongoing phase 1/2a clinical trial of Descartes-08, which showed that the therapy was well tolerated, with no evidence of cytokine release syndrome or other serious product-related adverse events. According to Cartesian, all patients experienced at least a full class improvement on the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification system. Patients also showed marked improvement on the Myasthenia Gravis Composite (MGC) scale, a standard measure of overall disease severity.  Cartesian reported mean improvement on the MGC scale of more than 50% about three months after Descartes-08 therapy.

“This was the first clinical trial of CAR T-cells for an autoimmune disease,” said Mozaffar. “Naturally, the first patients enrolled are some of our most severely affected and difficult-to-treat patients, who have been followed for many years. At this point, the results should be viewed only as case studies, but the two patients in the study who received Descartes-08 improved functionally to levels at which I have not seen before.”

According to Cartesian, Descartes-08 uses a novel modality and mechanism of action for treating generalized myasthenia gravis and other autoimmune diseases. It differs from anti-B-cell agents, which do not address long-lived plasma cells, and differs from FcRn blockers or complement inhibitors, which try to intervene only after the autoantibodies are produced and pathogenic mediators are amplified. Descartes-08 is intended to halt production of autoantibodies by targeting pathogenic long-lived plasma cells that can survive for decades within the body.

For more information about the Descartes-08 trial for patients with generalized myasthenia gravis and other stem cell clinical trials, contact the UCI Alpha Clinic at stemcell@uci.edu or call 949-824-3990.

The UCI Alpha Clinic is the clinical trials arm of the UCI Sue & Bill Gross Stem Cell Research Center and part of a network of the leading medical centers funded by the California Institute for Regenerative Medicine. It specializes in delivering leading-edge stem cell clinical trials and gene therapy to patients, and it seeks to accelerate the development of new treatments through partnerships with patients, medical providers and clinical trial sponsors. Visit stemcell.uci.edu to learn more about UCI clinical stem cell trials and regenerative medicine research.

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