Promising therapeutic approach for improving mitochondrial function

Scientists have made progress in the development of products that improve mitochondrial function, with a key milestone initiation of the first-in-human Phase I trial of its PPAR-delta (PPARd) modulator, MA-0211 (also known as MTB-1).

The study will assess the safety, tolerability, pharmacokinetics and pharmacodynamics of MA-0211 in healthy volunteers, which will provide the basis for a trial program in Duchenne Muscular Dystrophy (DMD) patients. MA-0211 is the first clinical compound to emerge from mitochondrial enhancement platform. The PPARd modulator aims to reverse the mitochondrial deficits in DMD, which play a key role in disease progression.

Scientists at  Mitobridge, Inc., have assembled extensive nonclinical data in patient samples and genetic animal models demonstrating that MA-0211 may be therapeutically beneficial to DMD patients. Treatment of DMD patient muscle cells with MA-0211 upregulated genes related to fatty acid oxidation, which increased mitochondrial function and mitochondrial biogenesis.

MA-0211 was evaluated in the widely used DMD mouse model, the mdx mouse, which has a point mutation in the dystrophin gene and recapitulates many of the deficiencies seen in DMD patients. Once-daily oral dosing of MA-0211 for five weeks in mdx mice produced several therapeutic benefits including increased running endurance on a treadmill, decreased muscle necrosis and inflammation and decreased diaphragm fibrosis. In a similar study, six months of dosing in older mdx mice resulted in decreased serum creatine kinase and improved cardiac and respiratory function compared to untreated mdx mice.