Mitobridge’s Novel Treatment Approach for Duchenne Muscular Dystrophy Advances into Clinical Development
- Category: Small Molecules
- Published on Tuesday, 08 August 2017 15:46
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First-in-Class PPARδ Modulator with Potential to Improve Mitochondrial Health
CAMBRIDGE, MA, USA I August 8, 2017 I Mitobridge, Inc., a pioneer in the discovery and development of products that improve mitochondrial function, today announces a key milestone with the initiation of the first-in-human Phase I trial of its PPAR-delta (PPARδ) 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 Mitobridge’s mitochondrial enhancement platform. The PPARδ modulator aims to reverse the mitochondrial deficits in DMD, which play a key role in disease progression.
DMD is a rare genetic disease caused by loss-of-function mutations in the dystrophin gene. This debilitating fatal disorder affects males and leads to progressive cardiac, skeletal and smooth muscle weakness and eventual loss of muscle mass. Mitobridge’s research has confirmed and expanded upon previous studies showing that mitochondrial defects contribute to abnormalities in the dystrophic muscle and play a central role in the etiology of DMD.
“PPARδ modulation represents a promising therapeutic approach to improving mitochondrial function and muscle health in DMD patients,” stated Mike Patane, CSO of Mitobridge. “This milestone with our lead program further validates our mitochondrial enhancement platform and ability to generate promising drug candidates that modulate mitochondrial function. Our research teams are actively evaluating MA-0211 in other diseases associated with mitochondrial dysfunction and developing other novel approaches to restoring healthy mitochondria.”
Mitobridge scientists 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. The strong pre-clinical data are the basis for advancing the compound into clinical development and highlight MA-0211’s potential to reverse key defects and slow disease progression. MA-0211 is being developed with the Company’s corporate partner, Astellas Pharma, Inc.
Recently, George Mulligan, Mitobridge’s SVP of Translation Medicine, presented an update of the MA-0211 program at the Parent Project Muscular Dystrophy Annual Connect Conference on June 30, 2017. The presentation is available here: https://youtu.be/leQnKrVm4YI.
MA-0211 (MTB-1), an orally bioavailable PPARδ modulator, is the first clinical compound to emerge from Mitobridge’s mitochondrial enhancement platform. In studies with patient muscle cells and animals, MA-0211 improves mitochondrial function, overall energy metabolism, muscle performance and regeneration. As DMD is characterized by mitochondrial defects, inadequate energy supply and muscle fibrosis, intervening with MA-0211 may be therapeutically beneficial for all DMD patients, regardless of their underlying dystrophin mutation. Additional clinical studies in other diseases characterized by mitochondrial deficiencies are currently being planned.
Mitobridge is dedicated to delivering therapeutics that improve mitochondrial function. Our team of experienced drug discovery and development scientists are leveraging their exceptional knowledge of mitochondria biology to develop a pipeline of innovative programs for the treatment of kidney and muscle diseases with high unmet medical need. Headquartered in Cambridge, MA, Mitobridge was launched in October 2013 with funding from Astellas Pharma, Inc., MPM Capital and Longwood Ventures. For more information about the Company, please visit www.mitobridge.com.