Monday, November 19, 2012

Heart, heal thyself: CIRM grantees find chemical that may stimulate heart stem cells to repair damage after an attack

heart muscle cells matured from embryonic stem cells,
courtesy of Sanford-Burnham Medical Research Institute
Here’s the dilemma a group of CIRM grantees near San Diego, CA set out to resolve: hearts contain stem cells, but those cells don’t always repair damage to the heart after a heart attack.

"They need to be stimulated," John Cashman told the San Diego Union Tribune. "They need to have a good reason to turn into heart cells." Cashman, from the Human BioMolecular Institute, is one of the authors of a new study published in the Journal of Medicinal Chemistry which identifies a chemical that might just provide that stimulation.

Sanford-Burnham’s Mark Mercola, who worked with Cashman, added: "Regeneration is thought to be an adaptive response to injury, but it just doesn't work all that well. The problem is that it needs to be goosed up." The group is working with the company ChemRegen to develop their chemical into a possible therapy.

The group found a chemical called IDT-1 that turns mouse and human embryonic stem cells in to heart cells in a lab dish. The idea is that this chemical might encourage stem cells in the heart to turn into heart muscle cells and repair damage that occurs after a heart attack. Basically, IDT-1 might goose those inactivated stem cells in the heart.

Writing for the Union Tribune, Bradley Fikes explains why getting from this promising chemical to human trials takes time. Mostly, it has to do with whether the drug is going to be safe. Sure, it prods stem cells to turn into heart cells, but what good is that if it also damages the liver, or causes other harm?
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.
Then, even if the drug is safe and effective in animal studies, there’s still the concern that older adults, who are most likely to have heart attacks, might not have sufficient numbers of heart stem cells to repair the damage, even if they are properly stimulated. Mercola called that the million dollar question.

These questions are why it’s important to be funding a range of possible techniques for treating heart disease. This page lists all the awards CIRM is funding that focus on approaches to treating the disease.


ResearchBlogging.orgSchade D, Lanier M, Willems E, Okolotowicz K, Bushway P, Wahlquist C, Gilley C, Mercola M, & Cashman JR (2012). Synthesis and SAR of b-Annulated 1,4-Dihydropyridines Define Cardiomyogenic Compounds as Novel Inhibitors of TGFβ Signaling. Journal of medicinal chemistry PMID: 23130626

1 comment:

  1. How Drug Company Money is Undermining Science

    The pharmaceutical industry funnels money to prominent scientists who are doing research that affects its products—and nobody can stop it

    By the mid-1990s, when Wyeth got caught in a patent battle over Premarin, Lindsay was a staunch Wyeth ally. He came out against approval of a generic version of the drug that would have cut into sales even though the generic form would have made it easier for osteoporosis patients to receive therapy. His reasoning was that such versions might not be precisely equivalent to the brand-name drug, a fact that can be true with certain drugs but was also a position that happened to echo the company line. “All we're asking is that we don't approve something now and regret it” later, he told the Associated Press in 1995. Lindsay's close relationship with Wyeth and other drug companies carried on for decades, in ways that were sometimes hidden. He started allowing Wyeth to draft research articles and began taking tens of thousands of dollars from pharmaceutical interests that stood to gain from his research.

    The scandal is not what Lindsay did so much as that his case is typical. In the past few years the pharmaceutical industry has come up with many ways to funnel large sums of money—enough sometimes to put a child through college—into the pockets of independent medical researchers who are doing work that bears, directly or indirectly, on the drugs these firms are making and marketing. The problem is not just with the drug companies and the researchers but with the whole system—the granting institutions, the research labs, the journals, the professional societies, and so forth. No one is providing the checks and balances necessary to avoid conflicts. Instead organizations seem to shift responsibility from one to the other, leaving gaps in enforcement that researchers and drug companies navigate with ease, and then shroud their deliberations in secrecy.

    “There isn't a single sector of academic medicine, academic research or medical education in which industry relationships are not a ubiquitous factor,” says sociologist Eric Campbell, a professor of medicine at Harvard Medical School. Those relationships are not all bad. After all, without the help of the pharmaceutical industry, medical researchers would not be able to turn their ideas into new drugs. Yet at the same time, Campbell argues, some of these liaisons co-opt scientists into helping sell pharmaceuticals rather than generating new knowledge.