Neuromuscular experts with the University of Miami Health System and the Miller School of Medicine will launch a Phase 1/2 clinical trial (NCT04146051) using the CAR-T drug, Descartes-08, to treat patients with generalized myasthenia gravis.
Generalized myasthenia gravis (GMG) is a rare disease and a chronic autoimmune condition in which auto-antibodies attack specific proteins at the neuro-muscular junction. This disrupts the way that nerves can communicate with muscles, resulting in muscle weakness and fatigue.
Descartes-08, an investigational therapy by Cartesian Therapeutics, is a CD8+ CAR-T product that targets cells expressing B-cell Maturation Antigen (BCMA), a protein expressed by all plasma cells. It is the first known CAR-T therapy to enter clinical development for autoimmune diseases, according to the company.
"Patients with severe GMG have limited treatment options and are often dependent on nonselective, chronic immunosuppressive therapies (ISTs) that have long-term toxicities," said Volkan Granit, M.D., principal investigator and assistant professor of neurology at the University of Miami Miller School of Medicine. "Cartesian's CAR-T technology selectively targets the primary culprit in the disease: antibody-producing plasma cells. Such selective targeting would be a first in GMG and could help patients discontinue use of chronic ISTs."
"An increasing trend in the treatment of myasthenia gravis is the development of more targeted therapies," said Michael Benatar, M.D., Ph.D., co-investigator on the study, professor of neurology and chief of the Neuromuscular Division at the Miller School of Medicine. "The strategy of targeting for elimination, the aberrant long-lived plasma cells that produce these autoantibodies with CAR-T cells, is a novel and very promising approach."
Men and women are impacted equally by myasthenia gravis, and it can occur at any age and in any race. The disease impacts almost 200,000 patients in the United States, Europe and Japan. Those living with GMG can experience a variety of symptoms, including drooping eyelids and double vision as well as severe muscular weakness that can result in life-threatening weakness of muscles of respiration.
The Neuromuscular Division in the Miller School's Department of Neurology is home to the largest myasthenia gravis clinic in the region, with multiple specialists dedicated to providing world-class care for patients with this rare autoimmune disorder, and also providing opportunities for MG patients to participate in groundbreaking research.