Drugs Regrow Heart After Heart Attack
2-Drug Therapy Regenerates Damaged Hearts in Animal Study
Oct. 9, 2006 -- It's not supposed to happen in mammals. But a two-drug treatment makes rat hearts regenerate after heart attacks.
The treatment is the brainchild of Felix Engel, PhD, of Children's Hospital Boston and Mark Keating, MD, now at the Novartis Institutes for Biomedical Research.
Engel and Keating note that the hearts of some lower animals repair themselves when damaged. But mammal hearts don't regenerate -- they only develop scar tissue. Until now.
Last year, Engel and Keating reported that they could make mammalian heart cells grow if they gave them two treatments. One is a drug that inhibits a chemical signal -- p38 MAP kinase -- that keeps heart cells from growing. The other is a drug called FGF1, which stimulates the growth of new blood vessels.
Now Engel, Keating, and colleagues report that they can use the two-drug therapy to regenerate the hearts of rats that have had heart attacks.
"Regeneration is not just making more [heart-muscle cells]," Engel says in a news release. Heart-muscle cells "need a blood supply and oxygen to survive. FGF1 … was providing a new blood supply. If you just inhibit p38 MAP kinase, you don't get new blood vessels."
If this all sounds futuristic, it is -- at least for now. There are two major obstacles to trying this treatment in heart attackheart attack patients.
The first obstacle is that the rats were treated immediately after heart attacks. People usually sustain heart damage over time. A useful treatment would have to reverse relatively longstanding heart damage.
The second obstacle is that both of the drugs used in the study could be harmful. FGF1 stimulates the growth of new blood vessels for heart cells -- but would also stimulate the growth of cancercancer cells. And p38 MAP kinase inhibitors can damage the liver. That means that for now, researchers would have to find a way to keep both drugs from leaving the heart.
Eventually, the goal is to find treatments that work the same way but affect only the heart. Indeed, Engel and colleagues already are on the trail of a new drug that stimulates the growth of heart-muscle cells.
"In the end, we'd like a treatment that could be given systemically," Engel says. Systemic drugs travel throughout the body.
The findings appear in the Oct. 9 early online edition of the Proceedings of the National Academy of Sciences.