Pipeline & Programs:Pipeline

Phase I/II

Molecule: Biologic

Mechanism: In Duchenne, the absence or near-absence of the protein dystrophin leads to muscle membrane instability and disruption of the dystrophin glycoprotein complex (DGC). Microdystrophin is a synthetic version of the dystrophin gene that is believed to retain its key components and functionality. In preclinical models, therapeutic administration of microdystrophin by adeno-associated virus (AAV) has been shown to stabilize the DGC and restore muscle function.

Impact on Duchenne: The large size of the dystrophin gene has historically prevented direct replacement as a therapeutic strategy. Preclinical studies have shown that microdystrophin AAV-mediated gene transfer enables systemic delivery of the truncated gene and has the potential to slow or halt disease progression, regardless of the type of dystrophin gene mutation.

Preclinical

Molecule: Biologic

Mechanism: Muscular dystrophy is characterized by the replacement of muscle with non-functional fibrotic tissue, which is caused by inflammation and muscle degeneration. The goal of this program is to target a known mediator of fibrosis, TGF-β, and inhibit its activity. We believe this may be accomplished by targeting a protein known as the latent TGF-β binding protein 4 (anti-LTBP4).

Impact on Duchenne: Anti-LTBP4 has been identified as a genetic modifier of Duchenne and has been associated with a delayed loss of ambulation. Through the ability of this protein to reduce TGF-β activity, anti-LTBP4 activation has the potential to reduce fibrosis in Duchenne patients and slow functional decline.