Model MuSK-CAART - Potential Treatment Under Development for Patients with Myasthenia Gravis (MG)

MuSK-CAART Strikes a Hopeful Note for Patients with MG

MuSK-CAART targets B cells that produce autoantibodies against muscle-specific kinase (MuSK), a transmembrane protein found in muscle cells that is required for the formation and maintenance of the neuromuscular junction.

MG is an autoimmune disease caused by autoantibodies targeting parts of the neuromuscular junction, leading to motor impairment, shortness of breath, disabling fatigue, and episodes of respiratory failure. Generalized MG, or gMG, affects approximately 50,000 to 80,000 patients in the United States.

gMG can be classified into two primary types:

• AChR MG (affects ~85% of patients with gMG) – B cells produce autoantibodies against the acetylcholine receptor (AChR). Patients are typically treated with acetylcholinesterase inhibitors.
• MuSK MG (affects ~6% to 7.5% of patients with gMG) – B cells produce autoantibodies against MuSK, a transmembrane protein on the surface of the muscle membrane. These patients typically do not respond to acetylcholinesterase inhibitors and are treated with corticosteroids, generalized immunosuppressants, and in cases of severe disease, intravenous immunoglobulin and rituximab. However, these methods are associated with relapse and often, ongoing dependence on corticosteroids.

The activity of MuSK-CAART was evaluated in an animal model in comparison to CART19 cells, where they demonstrated specific in vivo target engagement through elimination of anti-MuSK target cells.¹ Further studies to enable an IND application are currently ongoing.

MuSK-CAART has shown promising preclinical results, with in vitro demonstration of selective and specific target engagement¹. Additional in vitro studies, including evaluation with a membrane protein array incorporating ~6,000 human proteins, has shown no off-target toxicity to date.