The following interview with Kevin Strange, Ph.D., president of the MDI Biological Laboratory, is excerpted from Eureka, a blog serving the CRO (contract research organization) industry. Launched by Charles River Labs in 2012, the site is a way for scientists to connect and share big ideas on the cutting-edge bench science driving drug discovery and development, particularly in the areas of preclinical safety and assessment, pharmaceutical manufacturing and animal research models. Later this month, Strange will be among the dozens of industry leaders to present their thoughts on the future of translational medicine at the Inaugural Charles River World Congress on Animal Models in Drug Development, which will explore how to use clinical data to develop translatable models for drug discovery.
If your pet mouse has a heart attack, zoologist Kevin Strange is quite certain he can help you.
Strange is President and CEO of the Mount Desert Island (MDI) Biological Laboratory in Bar Harbor, and co-founder of MDI’s spinoff Novo Biosciences, which is developing small molecules that reactivate and stimulate innate healing abilities in humans and animals.
One of those drugs, called MSI-1436, is a naturally occurring aminosterol (an antimicrobial agent) that inhibits protein tyrosine phosphatase 1B, a negative regulator of leptin and insulin signaling pathways.
MSI-1436 was initially developed as a diabetes drug. But it turns out that MSI-1436 also stimulates regeneration of heart and other tissues in different animals, including in mice where an injection of the drug candidate into the rodent’s stomach cavity, four weeks after induction of a heart attack, not only improved heart function and reduced dead tissue but reduced ventricular wall thinning and increased the proliferation of cardiac muscle cells. (The findings were published this year in NPJ Regenerative Medicine.)
What makes these findings even more interesting is that the drug candidate’s regenerative potential was identified using adult zebrafish as the screening platform. A phenotypic screen identified potential candidates that could stimulate tissue regeneration, and MSI-1436, in a blinded, randomized trial was ultimately found to stimulate the rate of regeneration of tail fin tissue and heart muscle without tissue overgrowth or malformations. In this regard, zebrafish are far more versatile than we humans who, with the exception of newborns, have few options beyond a transplant, when our hearts fail.
Strange says for the past 15 years, the field of regenerative medicine has been trying, with little success, to overcome heart failure with human stem cell-derived therapies. Yet nature is filled with animals, including zebrafish that readily generate lost and damaged body parts, including cardiac tissue, says Strange, who will be speaking about alternative models at the World Congress on Animal Models meeting sponsored by Charles River in Boston this Fall.
With the exception of newborns, where the human heart can regenerate, most of us lack the capacity to do what zebrafish can, adds Strange. Zebrafish hearts are also more similar to the human heart than a mouse heart, he says, which made them an ideal alternative model to test out their theory.
Strange says his group remains cautiously optimistic as they move MSI-1436 to the next level of testing. “The fact that MSI-1436 worked in zebrafish and mice, which are separated by 400 million years of evolution, that we know the target and understand why inhibition of the target stimulated regeneration represent huge steps forward.”