Novel small molecule for the prevention and treatment of DMD cardiomyopathy

The National Heart, Lung, and Blood Institute awarded Novomedix LLC $355,963 on September 1, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to develop and test novel small-molecule anti-fibrotic compounds for prevention and treatment of Duchenne muscular dystrophy cardiomyopathy.

The project addresses cardiac complications in DMD patients, where improved respiratory support has extended survival into the second and third decade of life but exposed an unmet need for heart-failure interventions. Novomedix will conduct preclinical studies in a DMD mouse model to evaluate protective effects of novomedix small molecules against cardiac fibrosis, systolic and diastolic dysfunction, and cardiomyocyte death. The work includes selection of two to three lead compounds for in vivo testing and investigation of chronic anti-inflammatory and anti-fibrotic mechanisms through suppression of specific inflammatory and metabolic pathways including NLRP3-inflammasome, TGF-β/IL-11, and AMPK/mTOR signaling.

The award is structured as a Project Grant, the assistance type for investigator-initiated research. Performance of the work is located in San Diego, California, with a period of performance from September 1, 2026, through July 31, 2027. Novomedix LLC is a woman-owned small business focused on novel small-molecule therapeutics for complex medical conditions including cardiovascular disease and fibrotic disorders.

Abstract

Duchenne muscular dystrophy (DMD) is the most frequently inherited and devastating human disease of muscle tissue leading to severe muscle weakness. This progressive disease generally affects young boys who usually present with symptoms between 3-5 years of age, primarily involving skeletal muscles, but also affecting the heart muscle. Several mechanisms for disease progression have been identified, including muscle cell death, inflammation, and disruption of energy generation. Respiratory failure has long been the leading cause of death in boys with DMD, however, with the advent of respiratory therapy and support, patients with DMD may now survive beyond the 1ST decade to unfortunately DIE in the 2ND or 3RD decade of life from heart failure. This represents an unmet need to better understand the mechanism(S) leading to heart failure in DMD patients in order to develop novel, effective treatment approaches. Recently, the role of novomedix (NMX) small anti-fibrotic molecules in protection of the heart and other organs against failure has placed this class of novel molecules as strong candidates for treatment of cardiovascular disease. In this application, we have proposed conceptually innovative studies, using a mouse model of DMD and novel NMX compounds, that will delineate the role of attenuation of sterile inflammation, cardiomyocyte death and increased fibrosis in mitigating heart failure in DMD. We will test the following hypotheses: 1) selection of 2-3 compounds for in vivo studies; 2) to investigate the protective effects of NMX in an established mouse model of DMD by studying the impact of NMX on cardiac fibrosis and LV systolic and diastolic function in male D2.B10-dmdmdx/J (D2-MDX) mice up to 9 months of age, and determining the chronic anti-inflammatory and anti-fibrotic mechanism of NMX therapy, through suppression of NLRP3-inflammasome, TGF-/IL-11, and ampk/mtor pathways in attenuating the evolution of DMD-CM. We will also determine whether primary cardiomyocytes isolated from DMD mice are progressively more primed for NLRP3 inflammasome activation compared to age-matched wild type mice. These studies will be the first to demonstrate the protective effects of NMX for prevention of DMD-CM, possibly through attenuation of inflammasome-mediated maladaptive signaling. This is especially novel and these findings may have a significant impact on decreasing heart failure progression in DMD patients while simultaneously improving their life expectancy.