Gladstone Institutes researchers use genetic clues to identify possible drug for treating heart conditions

In early lab and animal tests, the medicine appears to prevent the hardening of heart valves.

ByDan Ashley and Tim Didion KGO logo
Monday, February 1, 2021
Researchers use genetic clues to identify possible heart drug
On Thursday, researchers at the San Francisco-based Gladstone Institutes announced that research they have conducted on congenital heart disease has helped them to identify a possible drug for treating these conditions.

SAN FRANCISCO (KGO) -- On Thursday evening, a group of Bay Area researchers announced that they may have identified a potential drug for a debilitating heart condition.

Clues to the new medicine's structure came in part from families with secrets hidden in their genes.

Carmen Barron and her kids were in on the first page of what's become a decade long detective story.

ABC7 first met the Barron clan when they agreed to donate skin and blood samples to Dr. Deepak Srivastava, M.D., who is now president of the Gladstone Institutes in San Francisco.

The procedure was the beginning of research into rare congenital heart conditions, like the disease that's affecting at least twenty members of this extended Texas family.

"It was important for me to understand why," Barron says.

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Dr. Srivastava's team used a Nobel Prize-winning technology pioneered by Gladstone researchers that first turning the skin samples into stem cells.

From there, the research team turned those stem cells into living heart cells.

Given those cells were identical to the heart tissue of each family member, the team began probing for clues in the family DNA.

"That's how we were basically able to scan their own genome, of everybody in the family, and find a single gene," says Srivastava. "A mutation in a single gene that was responsible for their disease."

But the study didn't stop with the Barron family.

Over more than a decade, Srivastava's team has followed a genetic trail, paved with information gleaned from similar families and individuals with a variety of genetic heart conditions.

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In a new breakthrough, they have homed in on a specific condition, responsible for tens of thousands of heart surgeries every year through hardening of valves in the heart.

"And that put us on a path to what we most recently reported," Dr. Srivastava explains. "Which is we took the knowledge of the mechanism by which the disease occurs and then used that to screen for a drug."

Using artificial intelligence and help from collaborators in Russia, the Gladstone team identified a single drug candidate.

In early lab and animal tests, the medicine appears to prevent the hardening of heart valves.

This phenomenon has not only been seen in tissue with the specific genetic mutation, but offers hope for potentially thousands of other patients as well.

"It might be the kind of drug people would take for a long period of time to prevent this from happening when they get older," Srivastava believes.

If successful in human trials, the doctor adds the drug could potentially be used to reverse disease, or perhaps be given to expecting mothers prior to birth in a strategy to control damage from congenital heart defects.

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Since part of the Barron family's heart defect involves hardening of heart tissue, the drug could possibly benefit them.

Carmen Barron further explains the information they gained from participating in the Gladstone study, coupled with advances in in-vitro fertilization, is also giving her children new options for genetic screening.

This knowledge could possibly allow them to avoid passing the dangerous gene onto their own future families.

"My daughter, hopefully praying, will be able to start that process and have a healthy child," says Barron.

The Gladstone team is now hoping to move the drug candidate into human trials.