JHU Ref #: C17163
Value Proposition
· Improves specific isometric force and muscle-fiber cross-sectional area.
· Reduces necrosis and inflammation in early disease, as well as diaphragm fibrosis in advanced disease.
· Doubles the proportion of dystrophin-positive fibers and nearly doubles functional endurance when combined with AAV gene therapy, highlighting its add-on/synergistic potential.
· Safe and convenient once-daily oral dosing, supported by over 20 million patient-years of post-marketing safety data in the treatment of type 2 diabetes.
· Patent-pending applications for use in DMD/BMD, both as a stand-alone therapy and in combination with gene and antisense therapies.
Unmet Need
· Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disease that affects approximately 1 in 5,000 newborn boys (360 births per year in the U.S.) and about 12,000 prevalent patients in the U.S. Several treatments have been developed, including steroids, exon-skipping drugs, and AAV gene therapies. Although these treatments help slow disease progression, they do not regenerate muscle or reverse fibrosis. Thus, there is a strong need to develop therapeutics that enhance and complement existing treatments for patients with DMD.
Technology Description
· Current methods for treating DMD slow disease progression and manage symptoms but remain ineffective at curing the disease. Researchers at Johns Hopkins showed that pioglitazone (Pio) re-programs dystrophic macrophages toward a growth-factor-expressing, anti-fibrotic state, expands regenerative inflammation zones, and drives new myofiber formation across disease stages. Because pioglitazone is already FDA-approved, it can reduce development costs and timelines by more than 50% through the 505(b)(2) and Orphan Drug pathways. Pioglitazone can be deployed as a stand-alone therapy in early-stage disease or as a combination enhancer with exon-skipping therapies, SRP-9001 gene therapy, or CRISPR editing in later stages.
Stage of Development
· In vivo studies have been completed in a murine preclinical model of DMD (D2.mdx mouse), demonstrating improvements in muscle regeneration and function, including the development of new muscle fibers even in later fibrotic stages.
· Preclinical efficacy has also been demonstrated in late-stage D2.mdx mice when used in combination with AAV-microdystrophin.
Data Availability
· Comprehensive datasets and a study report are available upon request.
Publication
N/A
