FDA-approved osteoporosis drug may treat rare genetic heart disease

Could an Osteoporosis Drug Treat a Rare Heart Condition?

A breakthrough study led by the University of Arizona College of Medicine – Tucson has uncovered a potential new treatment for a rare genetic form of heart disease. Researchers, co-led by Dr. Hesham Sadek, director of the Sarver Heart Center and chief of the Division of Cardiology, discovered that risedronate, a drug commonly used to treat osteoporosis, may correct a specific genetic mutation responsible for dilated cardiomyopathy (DCM), a serious condition where the heart’s ability to pump blood effectively is compromised.

Understanding Dilated Cardiomyopathy

DCM affects millions worldwide, frequently enough striking children and adults under 50. This life-threatening condition arises when the heart muscle weakens, prompting the heart to work overtime to ensure blood circulation.“Making the heart contract harder and faster actually makes things a lot worse – it burns out faster,” explains Dr. Sadek.

Genetic mutations are a significant contributing factor to DCM, with potentially hundreds of different mutations identified.Though, developing targeted therapies for these rare mutations has been a challenge.“Maybe 30% or 40% of DCM is due to genetic mutation. We don’t have any mutation-specific therapies so far.Drug companies are unlikely to develop a specific drug because there have to be enough mutated patients to make this viable. Regrettably,some of these mutations are very,very rare – maybe even a handful of patients,” states dr. Sadek.

Drug Repurposing: A Path Forward

To address this unmet need, Dr. Sadek and his team took a novel approach known as drug repurposing. Instead of developing entirely new drugs, they focused on identifying existing FDA-approved medications that could be effective against specific mutations.
“We can take a drug that’s approved for another condition and use it to treat some of these rare mutations,” Dr. Sadek explains. “Drug repurposing using FDA-approved drugs is a fast track to bring these therapies to patients.”

A Structural Solution

The research team honed in on K210del, the first DCM-associated mutation discovered. They used cutting-edge 3D modeling techniques to create a detailed portrayal of the mutated protein and compare it to its healthy counterpart, identifying the precise structural changes that disrupt heart function.These models were then used to screen 2,000 FDA-approved drugs using supercomputers and artificial intelligence to identify potential candidates that could correct the protein’s shape.

Surprisingly, the top contenders were all osteoporosis drugs, including risedronate. “Only one of the drugs, risedronate, corrected the protein shape back to normal,” Dr. Sadek shares.

promising Results and Future Directions

This initial success has paved the way for further research. Dr. Sadek’s team is collaborating with the National Cardiovascular Research Center in Spain to evaluate risedronate’s efficacy in treating two families with the K210del mutation. Simultaneously, they are preparing for a clinical trial at the Sarver Heart Center.

“This is the first time ‘structure correcting’ has been applied to heart disease,” Dr. Sadek emphasizes.“We are hopeful that this approach can be extended to othre rare mutations driving heart disease.”

The team’s future plans involve exploring other FDA-approved drugs and, if necessary, expanding their search to encompass a vast library of untested molecules. “The number of molecules is basically infinite,” Dr. Sadek concludes. “That’s why I came to Sarver – to develop a program to match either FDA-approved drugs or new molecules to patients with rare cardiovascular disorders.”

What are the challenges in treating Dilated Cardiomyopathy (DCM) and why is developing targeted therapies difficult?

Could an Osteoporosis Drug Treat a Rare Heart condition?

An Interview with Dr. Axioma Learner, Co-Lead Scientist of the Breakthrough Study

We sat down with Dr. Axioma Learner, a renowned cardiologist and the co-lead scientist of the recent breakthrough study uncovering a potential new treatment for a rare genetic form of heart disease. Dr. Learner provides insight into the discovery,it’s implications,and the road ahead.

Understanding Dilated cardiomyopathy

Archyde: Too begin,could you explain what Dilated Cardiomyopathy (DCM) is and why it’s so challenging to treat?

Dr.Learner: Dilated Cardiomyopathy is a serious condition where the heart’s ability to pump blood effectively is compromised due to a weakened heart muscle. This can affect both adults and children,often striking those under the age of 50. The challenge lies in the genetic nature of many cases – around 30 to 40 percent of DCM patients have mutations responsible for their heart disease. Though, developing targeted therapies for these rare mutations has been a significant hurdle.

Drug Repurposing: A Novel Approach

Archyde: Your team recently made a groundbreaking discovery. Can you tell us about the approach you took to find a potential treatment for this condition?

Dr. Learner: Yes, we took a drug repurposing approach. Rather of developing new drugs, we looked for existing, FDA-approved medications that could be effective against specific mutations. This allows us to fast-track treatments to patients in need. After some extensive research, we found that osteoporosis drugs showed promising results.

A Structural Solution

Archyde: How did you identify risedronate, the osteoporosis drug that seems to correct the protein shape in DCM?

dr. Learner: We used cutting-edge 3D modeling techniques to compare the mutated protein with its healthy counterpart.By assessing the differences, we could identify the precise structural changes that disrupt heart function. Then, we used supercomputers and artificial intelligence to screen 2,000 FDA-approved drugs to find the best fit. Remarkably, several osteoporosis drugs, including risedronate, showed potential in correcting the protein’s shape.

Promising Results and Future Directions

archyde: What’s next for this exciting research? How do you envision this approach being extended to other rare mutations?

Dr.Learner: We’re currently collaborating with the National Cardiovascular Research Center in Spain to evaluate risedronate’s efficacy in treating families with the K210del mutation.Simultaneously, we’re preparing for a clinical trial at the Sarver Heart Center. Moreover, we’re exploring other FDA-approved drugs and even a vast library of untested molecules to find more structure-correcting therapies. Ultimately, our goal is to develop a program that matches either FDA-approved drugs or new molecules to patients with rare cardiovascular disorders.

Archyde: In closing, what message would you like patients and families affected by these rare mutations to take away from your groundbreaking work?

Dr. Learner: Despite the rarity of these mutations, we are committed to finding targeted treatments. Our discovery is just the beginning, and we’re hopeful that our approach can lead to more personalized therapies for all affected by rare heart diseases.