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Tucson, AZ – A research team co-led by scientists from the University of Arizona College of Medicine – Tucson has made a groundbreaking discovery: an osteoporosis drug may counteract a rare genetic mutation linked to a specific form of heart disease. The study, published in the Journal of Clinical Investigation, opens new possibilities for treating rare cardiovascular disorders using existing medications.
A New Approach to Treating Dilated Cardiomyopathy
Dilated cardiomyopathy (DCM) is a condition characterized by weakened heart muscles, impairing the heart’s ability to pump blood efficiently. The American Heart Association reports that DCM primarily affects children and adults under 50, often leading to life-threatening complications.
“When the heart weakens, the body attempts to compensate by increasing its workload,” said Dr. Hesham Sadek, co-senior author and director of the Sarver Heart Center. “However, making the heart contract harder and faster actually worsens the condition.”
DCM is linked to various genetic mutations, but no mutation-specific therapies exist due to the rarity of some of these mutations. “About 30% to 40% of DCM cases are due to genetic mutation,” Sadek explained. “Unfortunately, some mutations affect only a handful of patients, making it financially unviable for drug companies to develop specialized treatments.”
Drug Repurposing as a Solution
Instead of developing a new drug from scratch, Sadek’s team explored repurposing existing FDA-approved medications. “If we find a drug that pushes a mutated protein back into shape, we could restore normal heart function,” he said.
The researchers focused on K210del, the first DCM-associated mutation identified. Using artificial intelligence and supercomputers, they screened 2,000 FDA-approved drugs to find one that could correct the flawed protein structure. Remarkably, multiple osteoporosis drugs showed potential, with one standing out: risedronate.
Encouraging Results and Future Trials
Risedronate successfully corrected the protein defect in lab tests and animal models. “For the first time in an animal model, we found an FDA-approved drug that can correct a gene mutation and normalize heart function,” Sadek stated.
The team is now collaborating with Spain’s National Cardiovascular Research Center to assess risedronate’s efficacy in two families with the K210del mutation. A clinical trial is also in the works at the Sarver Heart Center.
Sadek emphasized that this approach—correcting protein structures—has been used in cancer and cystic fibrosis research but is now being applied to heart disease for the first time. “Our goal is to identify FDA-approved drugs or novel molecules that can treat patients with rare cardiovascular disorders,” he said.
A Step Toward Broader Applications
Co-senior author Dr. Sakthivel Sadayappan highlighted the potential for expanding this approach to other rare genetic mutations. “If we don’t find suitable FDA-approved drugs, we can explore thousands of drugs that never made it to market, or even develop entirely new molecules,” he said.
The study’s findings could pave the way for a faster, more cost-effective path to treating genetic heart diseases, offering hope to patients with rare mutations who previously had limited options.
Reference: Wang et al. “An FDA-approved drug structurally and phenotypically corrects the K210del mutation in genetic cardiomyopathy models.” Journal of Clinical Investigation, 17 February 2025. DOI: 10.1172/JCI174081.
Disclaimer: This article is for informational purposes only and should not be considered medical advice. Patients should consult their healthcare providers before making any treatment decisions.
