When a worm is chopped in two, the missing part often re-grows. Researchers at several biotech companies are challenging the assumption that humans can’t perform a similar feat by developing drugs that encourage self-regeneration.
Hydra Biosciences is working a regeneration drug that stimulates heart muscle-cell regrowth, and could lead to better recoveries for heart attack sufferers. The protein-based drug induces mature cells to become a little bit like stem cells.
It causes heart cells to "dedifferentiate" partially, reverting them to an earlier stage of development and activating their ability to generate more muscle cells. Stem cells, by contrast, are fully undifferentiated, meaning they’re a clean slate and have the ability to turn into any type of tissue. But replacing damaged or diseased tissue by regenerating a patient’s own tissue, advocates say, has a leg up on stem cell-based procedures because it eliminates many potential medical problems, like immune rejection.
"Stem cell therapy involves using cells from outside the body, so there’s the potential for incompatibility," says Mark Keating, head of the human genetics division at the Novartis Institutes for Biomedical Research and an advisor to Hydra. "The cells can also divide too fast and become cancerous." He cautions, however, that it is too early to tell which of the two types of procedures will work best when tested in humans.
The biggest advantage to self-regenerative therapies, says Glenn Larsen, Hydra’s chief scientific officer, is that they capitalize on abilities the body already has. "Your body does a good job of regenerating itself normally," he says. "We’re just coming up with compounds that enhance that process."
Hydra is concentrating on regenerating heart muscle damaged by heart attacks when oxygen is cut off from large regions of the heart, leading to muscle-cell death. The dead cells are usually replaced by scar tissue, which can lead to congestive heart failure.
To test one of the proteins, called CRF1 (one of three Hydra is developing), researchers induced heart attacks in rats, then dosed them for 10 days. After about a month, the treated rats showed significant heart muscle function improvement compared to the untreated control group.
"The dogma has always been that heart muscle cannot regenerate," Larsen said. "But it’s possible in animals, and now we have drug candidates that may do the same thing in humans." He estimates human trials of the protein compounds will begin within the next few years.
Hydra hopes its cardiac-muscle drugs will prove to be just the tip of the regenerative medicine iceberg — the company is already considering investigating ways to re-grow retinas in macular degeneration sufferers and pancreatic cells in diabetics.
Other companies are starting to explore regenerative techniques as well. Genzyme, for instance, has developed a little-known drug called Carticel, which is FDA-approved to regenerate damaged cartilage and has proven useful in treating slow-healing knee injuries. Meanwhile, Epicell, in the United Kingdom, is developing ways to generate sheets of extra skin from the body’s own epithelial cells, techniques that are becoming instrumental in many types of reconstructive and plastic surgery.