Investigational Drug May Regenerate Tissue Following Heart Attack

An experimental drug may present patients who experienced a heart attack with a novel treatment option. The drug MSI-1436 has shown the potential to restore heart function in zebrafish and mice models, according to a study published by npj Regenerative Medicine.

Currently, no drug is able to restore heart function after a heart attack. If confirmed in humans, MSI-1436 could transform post-heart attack care, and improve patient outcomes.

"The potential impact of MSI-1436 is enormous," said study author Viravuth P. Yin, PhD. "If it shows similar results in humans, it will be a game-changer for patients who suffer a heart attack and/or are living with heart disease."

The authors are hopeful that the drug can move into human clinical trials soon; however, they must first test the drug in pigs, whose hearts closely resemble humans.

The drug may move quickly to clinical trials for 2 reasons. First, MSI-1436 stimulates tissue regeneration in the animal models, which is likely to be similar in humans. Second, the drug has already been well-tolerated in phase 1/1b clinical trials in humans for another condition. The maximum well-tolerated dose in humans was approximately 5 to 50 times higher than the dose effective in animal models, according to the study.

"The previous clinical trials of MSI-1436 make a big difference in bringing this drug to market," said study author Kevin Strange, PhD. "The path from laboratory bench to patient bedside can be long and difficult. But the fact that MSI-1436 has been shown to be safe for use in humans shaves years off the drug development process."

The authors have already received a patent on the use of the drug in patients with heart disease.

The original research was conducted among zebrafish, which have the ability to regenerate body parts. The authors discovered that administering MSI-1436 increased regeneration by 200% to 300%. Heart regeneration was also found to be as substantial, according to the study.

"That was definitely a 'Eureka!' moment," Dr Yin said in a press release.

The authors then conducted the study in zebrafish several more times under various conditions to confirm their findings, along with studies in mice, which have limited regenerative capabilities similar to humans. The goal of these studies was to determine if the drug could improve regeneration in other organisms.

While mammals are known to share the regenerative capabilities of zebrafish, these mechanisms have been widely deactivated.

In mice, the authors discovered that administering MSI-1436 after an induced heart attack increased survival, improved heart function 2- to 3-fold, reduced the size of scar tissue by 53%, reduced ventricular wall thinking, and stimulated heart muscle regeneration by 6-fold, according to the study.

When a patient experiences a heart attack, part of the muscle dies, resulting in scarring that impacts the heart’s function. The authors believe MSI-1436 is the first candidate to reduce scarring and improve heart regeneration in adult mammals.

The drug could also be used to regenerate skeletal muscle tissue in patients with Duchenne muscular dystrophy, and could be used for wound healing and other tissue regeneration.

"If we can decode the instruction manual for regeneration in highly regenerative species, we can use drug therapies to reignite our own dormant regenerative capacity,” Dr Yin concluded. “Our research in these highly regenerative species is showing that regenerating damaged or lost tissues and organs could be as simple as taking a drug."