With Gene Therapy, VentriNova Aims to Mend Broken Hearts

3/4/14Follow @benthefidler

When a baby is born, a pretty important type of gene shuts down. The gene that carries the instructions for making the heart does its job when the baby is in the womb, and it turns off when the baby is born. That gene is everything to a tiny New York-based startup named VentriNova, because it just might hold the key to repairing a damaged heart.

VentriNova, a startup based around the work of Icahn School of Medicine at Mount Sinai regenerative medicine director Hina Chaudhry, is attempting to develop a gene therapy procedure that would help regenerate cardiomyocytes, or muscle cells, in the hearts of patients who have suffered heart attacks. The idea is essentially in its infancy: VentriNova has only tested an early form of this gene therapy in preclinical animal studies, most recently in pigs. It is likely several years away from having the chance to prove the therapy works in humans in a big clinical trial. And plenty of other academics are trying to harness stem cell technologies to accomplish a similar feat. But Chaudhry says that VentriNova has been able to do something none of them have as of yet—produce new cardiac muscle cells in the injured heart of a large animal.

“There has been no approach to date that can actually create new cardiomyocytes in the diseased heart other than ours,” she says.

It’s the first significant step in what will be a long journey for Chaudhry’s VentriNova to show these findings can lead to a truly significant therapy, the kind that could be used to start to undo the damage caused by a heart attack.

VentriNova—a virtual company consisting of Chaudhry and acting chief operating officer Howard B. Johnson, one of the founding investors of Acorda Therapeutics—originally came together in 2006. That was when Chaudhry, then an assistant professor at Columbia University, was looking into genes that control the development of the heart. Since the genes that instruct the heart’s muscle cells to form are turned off at birth, they can’t be mobilized to turn back on and regenerate dead heart muscle after a heart attack. It’s not like other part of anatomy that are better at healing, like a cut on your skin. When the heart scars, it doesn’t recover.

Hina Chaudhry, scientific founder of VentriNova

Hina Chaudhry, scientific founder of VentriNova

“These genes are silent in the heart after birth,” she says. “This is the reason we have so much morbidity and mortality from heart attacks and heart disease. We can’t regenerate those tissues.”

Chaudhry wanted to find a way to switch that process back on again. She homed in on a gene, CCNA2, that expresses a protein called cyclin A2. First, she used transgenic mice to see what the difference would be if she flipped the switch, so to speak, and turned cyclin A2 back on. The genetically modified mice, she says, were showing signs of active cyclin A2 proteins. She then induced heart attacks in those mice, and saw evidence that even after heart tissue was damaged, new heart muscle cells were regenerating, she says.

That encouraged Chaudhry to try to create a company, and harness cyclin A2 for a therapeutic. She incorporated VentriNova, and turned to gene therapy to create a treatment. The plan is to load genetically engineered CCNA2 into a virus, and deliver it to the heart with an injection, where it can transmit the protein to the damaged area, and in theory, induce cells to divide.

The treatment would be delivered one of two ways. One option would be for doctors to … Next Page »

Ben Fidler is Xconomy's Deputy Biotechnology Editor. You can e-mail him at bfidler@xconomy.com Follow @benthefidler

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