New chemical may spur heart repair

Dead and damaged heart muscle may be replaced with stem cells from the heart itself, if a new chemical discovered by La Jolla-based scientists lives up to its promise.

The chemical, called IDT-1, turns mouse and human embryonic stem cells into an unlimited number of heart muscle cells, called cardiomyocytes. The scientists say it might yield a drug to repair damage from heart attacks and from cardiac fibrosis, or scarring in heart tissue.

A study on the findings was published Nov. 6 in the Journal of Medicinal Chemistry. Its authors include Dennis Schade and John Cashman of the Human BioMolecular Institute, along with Mark Mercola of the Sanford-Burnham Medical Research Institute.

The three are working with ChemRegen, a private La Jolla biotech company established by Cashman and colleagues, to see if a drug can be produced from the research.

If such a drug does emerge, it could become a blockbuster. Heart disease was the leading cause of death in the United States last year, with nearly 600,000 deaths, according to the U.S Centers for Disease Control and Prevention in Atlanta.

Hearts contain their own stem cells. While these cells could repair the damage from a heart attack, they don't, Cashman said.

"They need to be stimulated," he said. "They need to have a good reason to turn into heart cells."

The IDT-1 chemical blocks the activity of a substance called transforming growth factor-beta usually present in stem cells. This lack of activity starts the stem cells down the road into becoming heart cells.

But before ChemRegen can start clinical trials on a drug based on IDT-1, it must be tested for toxicity and taken through animal studies to see if it provides therapeutic benefit," Cashman said. All told, that may cost about $3 million to $4 million, with $1 million going for toxicology studies and the rest for animal studies. ChemRegen plans to seek partnerships with drug companies or other investors to fund that work.

IDT-1 is what the drug industry calls a small molecule, which has a relatively simple structure. In contrast, biotech products often are made up of large protein molecules, DNA, or even whole cells. Cashman said having a small molecule to work with should be a plus for pharmaceutical companies, because they're experienced in making such drugs.

Mark Mercola — Sanford-Burnham Medical Research Institute

"Making small molecules is less expensive than proteins and cells, and potentially less toxic," Cashman said. "Small molecules come and go. They're excreted in the urine. If you put DNA or a cell in the body, you can't pull it out. It's there for the rest of the organism's life."

Moreover, activating stem cells that already exist should be less problematic than other approaches, such as implanting heart muscle cells grown from stem cells, said Mercola, director of Sanford-Burnham's muscle development and regeneration program.

There's evidence that the heart stem cells naturally regenerate damage, Mercola said.

"Regeneration is thought to be an adaptive response to injury," Mercola said, citing evidence in mouse studies. "But it just doesn't work all that well. The problem is that it needs to goosed up."

However, it's an open question whether there are enough of these heart stem cells to significantly aid recovery from heart attacks in humans, Mercola said. Moreover, the number of these stem cells is known to decline with age -- and the heart regeneration experiments were conducted on young mice.

"What happens when you have heart attack patients, who are often in their 60s and 70s? Do they have this regeneration reserve? That's a million-dollar question," Mercola said.


