With Gene Therapy, VentriNova Aims to Mend Broken Hearts

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thread a catheter into a patient’s ventricle, map the area to find the damaged tissue, and inject the drug directly into it. Another idea is to inject it directly to the damaged areas of the heart—a procedure that would require surgery. VentriNova prefers the first approach, and will move forward with it assuming preclinical tests show it works just as well as a direct injection. The procedure would be done within three weeks after a patient has a heart attack, according to Chaudhry.

But while most everyone in gene therapy uses an adeno-associated virus (AAV) or a lentivirus to deliver their treatments, VentriNova selected an adenovirus as a vector. Chaudhry says this is for safety precautions: though she used an AAV vector on some pigs in her preclinical work, she saw that cyclin A2 was being expressed in other organs, including the liver. Because of these results, she says the potential toxicity issues in people are “more concerning” with an AAV than with an adenovirus because an adenovirus dies off in four to six weeks after treatment, whereas an AAV lasts much longer.

“If the virus lives forever it can go wandering into the wrong tissues. That is what we saw when we delivered the AAV to pigs,” she says. “With an AAV, you get lifelong expression of the virus and you get genome integration, so there could be all sorts of problems.”

Even so, Barrie Carter, the vice president who oversees gene therapy at San Rafael, CA-based BioMarin Pharmaceutical (NASDAQ: BMRN), is skeptical of the vector choice. He notes that AAVs have been used so far in a large number of trials and has shown “little to no toxicity,” and that its integration frequency is “actually very low.”

“The fact remains that there clearly is the potential for toxicities with adeno vectors,” he says. “All else being equal, I’d probably pick an AAV.”

Still, based on her findings so far, Chaudhry has been charging forward with the adenovirus. She tested the method in adult rats, and found similarly encouraging results: following a one-time dose administered after a heart attack, heart muscle cells in the rats began dividing, and common measures of heart strength, like its ability to pump out blood (referred to as ejection fraction), improved.

After a few years of “learn[ing] the ropes” of being a scientific entrepreneur, not just an academic, Chaudhry was able to get her work funded. The National Institutes of Health awarded her $500,000 in grant money in 2009, and Boston-based Broadview Ventures put in $1 million in equity financing shortly thereafter. That cash gave her the financial runway to conduct a large animal study at her current lab at Mount Sinai.

In the study, Chaudhry and other researchers induced heart attacks in pigs, and then administered either the cyclin A2 therapy, or a sham treatment, a week later. Researchers found a roughly 18 percent increase in the cardiac function of the pigs that underwent the therapy, compared to a 4 percent decrease in the cardiac function of the pigs that didn’t. Those results were measured six weeks after a single dose, according to Chaudhry.

Now, VentriNova can begin to head for the critical proving ground—clinical trials. VentriNova’s trying to raise about a $5 million Series A round to do bankroll all the preclinical work, such as toxicity and other studies, needed to get it in position to begin clinical trials. Chaudhry estimates it’ll be 18 to 24 months before VentriNova verifies its proof-of-concept study, completes its toxicity work, and gets the green light from the FDA to begin its first trial. Despite the journey ahead, and the wealth of competitors using stem cell technology, Chaudhry is optimistic that her approach will win out.

“I just think we have better results, and a more targeted approach that is based on what nature does as opposed to going against nature,” she says, referring to stem cell approaches. “This [therapy] is mimicking the pathways found in nature already.”

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