Organ regeneration with drugs

A drug that had been discarded reveals its ability to rebuild organs damaged by disease or injury.

IN SUMMARY

Stem cell treatments make headlines about healing and regeneration of various parts of the body, but they have had little success.

The compound MSI-1436 appears more promising, as indicated by animal experiments. It removes the brake on the body’s natural ability to regenerate cells.

The molecule, originally intended for the treatment of diabetes and obesity, successfully passed safety tests in people, a huge advantage in drug development.

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Regenerative medicine

An account of shark bites in a Scottish tavern opened us up to new ideas about rebuilding damaged organisms. At the beginning of this century, Georgetown University geneticist Michael Zasloff gave a lecture at the University of St. Andrews on various natural antibiotics found in animal skins. After the talk, he went to have a drink with other academics, and a marine biologist commented that dolphins were frequently attacked by sharks, causing huge injuries, 45 centimeters long and 12 centimeters deep. Surprisingly, the dolphins were cured within weeks, with no signs of infection.

Amazed by such speed to recover from excruciating injuries, Zasloff couldn’t stop thinking about that conversation. In the years that followed, he read reports on bitten dolphins and spoke with marine biologists who studied these animals. In 2011 he published a letter in the Journal of Investigative Dermatologyentitled “Observations on the extraordinary (and mysterious) wound healing of the bottlenose dolphin.” In it, he pointed out that the dolphins did not seem to just mend the tear with a scar, which produces other types of cells, but actually regenerated the damaged tissue. Soon after, he called one of us. Strange, then president of the Mount Desert Island Biology Laboratory (MDIBL) in Maine, was pushing for research into natural and synthetic compounds that stimulate regeneration, and Zasloff thought that some of the antibiotics he had discovered in animal skin also could encourage this kind of recovery. Anything that contributes to replenishing or restoring cells destroyed by disease or injury would be a medical breakthrough.

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Six years after that call, the three of us (Yin, Strange and Zasloff) have shown that the natural antibiotic MSI-1436, discovered by Zasloff in a small shark, intensely stimulates the regeneration of various damaged organs in zebrafish and the heart muscle. on the mouse. The compound releases certain molecular “brakes” that suppress the natural ability of tissue to regenerate after injury. In mice affected by the equivalent of muscular dystrophy in humans, it slows down the degeneration of the muscles. We are still experimenting with animals and have not demonstrated these effects in humans, but MSI-1436 has a significant advantage over the myriad compounds that show promise in the lab and then fail in people – it has already proven its safety.