Many serious inherited myopathies are marked by an exaggerated injury response with use. This includes Duchenne and Becker muscular dystrophy, and a family of limb girdle muscular dystrophies and metabolic myopathies.
Amongst these, muscle injury in the context of Duchenne is best understood. Skeletal muscle contraction leads to membrane stress and muscle fiber breakdown through excessive contractures and programmed cell death. We are designing strategies to stabilize patient skeletal muscle so that muscle use is uncoupled from its excessive injury response. Our approaches do not rely on dystrophin replacement so will be applicable for patients with any dystrophin mutation and in combination with all approved and experimental therapies for this disease.
Our lead program is progressing through preclinical safety studies and with appropriate results, we expect to file an investigational new drug (IND) application with the U.S. Food and Drug Administration in 2020. Initial clinical studies will be conducted in healthy volunteers, followed by clinical studies in patients.
Areas of Focus
Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a severe, incurable degenerative muscle disease that affects about one in 5,000 males at birth. It is the most common type of muscular dystrophy and is caused by absence of dystrophin, a large protein that connects muscle contraction to the supporting basement membrane around muscle fibers. Young patients are ambulant but become wheelchair bound in their teen years and have a shortened lifespan, generally to the third decade of life with death from either respiratory or cardiac failure.
Becker Muscular Dystrophy
Becker muscular dystrophy (BMD) is a milder form of DMD, mostly affecting boys. It is caused by mutation of dystrophin that results in truncated of the protein. The disease is variable and can range from mild to almost as severe as the symptoms of DMD. Patients usually have weakness of the hips and pelvis and may have problems walking by their late teens. Disability and heart problems are common in these patients.
Adult Neuromuscular Diseases
Edgewise is also developing medicines for additional muscle disorders common in adults. These include slower-onset forms of inherited muscle myopathies such as Limb Girdle Muscular Dystrophies (LGMD) and movement disorders that include spasticity and contractures resulting from multiple sclerosis, spinal cord injury or stroke.
Edgewise Therapeutics Pipeline
Edgewise builds on our extensive experience in drug development and skeletal muscle research. We have built a custom discovery workshop for the discovery and optimization of novel therapeutics for a broad set of indications where skeletal muscle function is compromised. This includes enzymology and high throughput biochemistry, unique capabilities in skeletal and cardiac muscle physiology and in vivo pharmacology, including a broad array of techniques for assessing physical function. Our facilities take maximal advantage of our location within the BioFrontiers Institute, a pioneering interdisciplinary hub within the University of Colorado designed to house both Academic and Industrial research.