MDI Biological Laboratory researchers receive patent for novel heart disease drug

The U.S. Patent and Trademark Office has announced that it will grant a patent to MDI Biological Laboratory scientists Voot P. Yin, Ph.D., and Kevin Strange, Ph.D., and their collaborator Michael Zasloff, M.D., Ph.D., for use of the small molecule MSI-1436 to stimulate the repair and regeneration of heart tissue damaged by injuries such as a heart attack.

The patent award -- the first for the MDI Biological Laboratory -- represents a major step forward in moving MSI-1436 into clinical studies in humans. The MDI Biological Laboratory, located in Bar Harbor, Maine, is an independent, non-profit biomedical research institution focused on increasing healthy lifespan and increasing our natural ability to repair and regenerate tissues damaged by injury and disease.

In 2013, Strange and Yin spun off the MDI Biological Laboratory's first for-profit company, Novo Biosciences, with the central goal of developing MSI-1436 into a novel therapeutic for treating heart and skeletal muscle diseases. The MDI Biological Laboratory has granted Novo Biosciences an exclusive license to develop MSI-1436 as a regenerative medicine therapy.

"The importance of this achievement cannot be overstated," said Strange, president of the MDI Biological Laboratory and co-founder and CEO of Novo Biosciences. "This patent is a critical step forward in our ability to develop new treatments for those who suffer from heart disease, as well as a validation of the effectiveness of MDI Biological Laboratory's and Novo Biosciences' approach to drug discovery and development."

MSI-1436 can potentially be used to stimulate the formation of new heart muscle after an acute heart attack. Because humans have a limited capacity for heart tissue regeneration, damaged heart muscle is normally replaced with a nonfunctional scar. This scar tissue interferes with the function of the heart and can lead to severe disability and ultimately heart failure. Currently, there are no approved treatments to stimulate the regeneration of heart muscle in humans after a heart attack.

Another potential use of MSI-1436 under development is for the treatment of muscular dystrophies. Duchenne muscular dystrophy is the most common form of the disease and is characterized by progressive muscle degeneration and ultimately death due to heart and/or respiratory failure.

"Much of the current research in regenerative medicine focuses on highly complex stem cell therapies and tissue engineering strategies," Strange said. "Our research demonstrates that repairing tissues may be as simple as taking a pill that activates our innate repair mechanisms. Because of the ease with which they can be administered, pharmacological strategies hold the promise of dramatically increasing access to therapies for tissue and organ repair."

The potential market for MSI-1436 is enormous. Heart disease is the leading cause of sickness and death worldwide, accounting for approximately 17 million deaths per year. Of these deaths, about 7.4 million are due to coronary heart disease, the most common form of the disease. About 720,000 people experience a heart attack annually in the United States, which means that hundreds of thousands people each year could benefit from a therapy to repair and regenerate damaged heart muscle tissue.

The research on MSI-1436 was conducted by Yin, an assistant professor at the MDI Biological Laboratory and co-founder and chief scientific officer of Novo Biosciences. Yin conducted his initial research in zebrafish, which share 70 percent their genes with humans. Though humans possess the same genes required for the regeneration of heart tissue in zebrafish, human heart tissue does not regenerate after an injury for reasons that aren't clearly understood.

"The zebrafish heart robustly regenerates missing or damaged tissue in as little as 30 to 60 days," Yin said. "Humans share the same genetic material required by zebrafish for heart regeneration. Our goal has been to understand the molecular mechanisms underlying the repair and regeneration of tissues in zebrafish so that we can identify drugs like MSI-1436 that will reawaken dormant genetic programs and activate our own innate repair mechanisms."

Follow-up studies in mice, which are similar to humans in having a limited capacity for regeneration, demonstrated that the administration of MSI-1436 24 hours after an artificially induced heart attack greatly increased survival, tripled the proliferation of heart muscle cells at the border of the area of tissue death, doubled the improvement in heart function, reduced ventricular wall thinning and reduced the amount of scar tissue by 53 percent four weeks after the heart attack.

"If MSI-1436 shows similar results in humans, it will be a game-changer for patients who suffer a heart attack and/or are living with heart problems," commented Yin.

A major advantage of MSI-1436 for commercialization is that it has already undergone extensive clinical testing. Phase 1 and 1b clinical trials in 2007 for an unrelated disease have demonstrated that MSI-1436 is well tolerated by humans. The doses that were effective in inducing heart repair and regeneration in mice were 50 times lower than the maximum safe human dose.

In addition to acute heart attack and muscular dystrophy, MSI-1436 also holds potential for the stimulation of wound healing, the reduction of wound scarring and the regeneration of multiple other tissues, including nervous tissue.