A study by UT Southwestern Medical Center has demonstrated that a combination of FDA-approved drugs can effectively regenerate damaged heart muscle.

Summary: UT Southwestern Medical Center researchers have found that two FDA-approved drugs, paromomycin and neomycin, can regenerate heart muscle and improve cardiac function post-injury. The study showed these drugs, when used together, target proteins that inhibit heart muscle regeneration. Initially used to treat bacterial and parasitic infections, these drugs demonstrated in animal models that they could effectively reduce heart scarring and enhance systolic function. This could lead to advances in treating heart failure, a condition affecting 30 million people worldwide. The findings suggest potential human clinical trials could commence soon given the drugs’ established safety profiles.

Key Takeaways:

  • Paromomycin and neomycin, FDA-approved antimicrobials, have shown promise in regenerating heart muscle and improving cardiac function in animal models following heart injuries.
  • The drugs work by inhibiting the proteins Meis1 and Hoxb13, transcription factors that normally block heart muscle regeneration after birth. This pharmacological targeting reactivates the heart’s intrinsic regeneration capability.
  • The success of paromomycin and neomycin in animal studies, alongside their established safety profiles as FDA-approved drugs for other uses, sets the stage for potential human clinical trials aimed at treating heart failure, according to the researchers.

Heart failure patients may one day be able to restore cardiac function with medications that revive the body’s ability to regenerate heart muscle, a study at UT Southwestern Medical Center suggests.

Heart failure affects close to 30 million people worldwide. An underlying cause is the inability of the adult myocardium—the muscle layer that helps the heart pump blood—to regenerate after injury, such as a heart attack.

In a study published in Nature Cardiovascular Research, a team from UT Southwestern demonstrated that two US Food and Drug Administration-approved drugs, paromomycin (Paro) and neomycin (Neo), improved left ventricular systolic function and decreased scar formation in both small and large animal models after a cardiac injury. 

Cardiac Recovery with Repurposed Drugs

The medications, when given in combination, target two proteins that regulate the heart muscle’s regeneration capabilities.

“Our study suggests that pharmacological targeting of the transcription factors Meis1 and Hoxb13 can be a viable therapeutic option for patients with heart failure,” says study leader Hesham Sadek, MD, PhD, professor of internal medicine in the division of cardiology and associate director of the Hamon Center for Regenerative Science and Medicine at UT Southwestern, in a release. “Heart muscle regeneration is present in mammals in utero and for a brief window of time after birth but is lost shortly thereafter because it is blocked by Meis1 and Hoxb13. By inhibiting the transcriptional activity of these proteins with a combination of Paro and Neo, we can induce cardiac muscle replication and stimulate heart regeneration.”

Paro and neo are naturally occurring antimicrobials used to treat parasitic and bacterial skin infections and to decrease the risk of infection after intestinal surgery, among other indications. The drugs were identified from a group of hundreds of potential medications via the study group’s unique platform for detecting FDA-approved drugs that can be repurposed to target new diseases. 

From Lab to Clinic: The Journey of Paro and Neo

Paro and Neo were then tested on animals to determine their effectiveness. The researchers discovered that combining the drugs was most effective in turning off the proteins’ regulation of cell growth. Importantly, the effectiveness of these two drugs in inducing regeneration in large animals holds promise for their potential use in human clinical trials. 

The findings build on more than a decade of research at UT Southwestern to identify the capacity of the heart to regenerate myocardial muscle. Earlier studies looked at factors that mediate loss of this regenerative capacity, including the identification of Meis1 and Hoxb13 as key regulators. The latest study is the first to show a drug combination that can induce heart regeneration in small and large mammals.

“The fact that these are FDA-approved drugs with established safety profiles makes it much easier to start testing this in humans in the near future,” says Sadek, who is also professor of biophysics and molecular biology at UT Southwestern, in a release. “Further studies can help us better understand the efficacy of pro-regenerative therapeutics and accelerate their delivery to the clinical setting.” 

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