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July 10, 2017 Focus: Bioscience

UConn biologist takes new tack against herpes virus

PHOTO | Contributed Sandra Weller, chair of UConn Health's molecular biology and biophysics department, is using state-funded molecular screening services to identify potential treatments for the herpes virus.

Herpes is more common than you might think.

The virus' various forms affect most people, though they are often unaware. Herpes can remain dormant in healthy people but sometimes lead to serious or fatal conditions in infants or those with weak immune systems.

While there are no cures for the various forms of herpes, antiviral drugs do exist to curb its effects but there is a constant search for new remedies.

Among the researchers searching for answers is UConn Health biologist Sandra Weller, who chairs UConn's molecular biology and biophysics department. Her lab is researching treatments for a form of herpes called Cytomegalovirus, or CMV, which can cause serious problems in newborns, including developmental disabilities and deafness, as well as infections in organ and marrow transplant patients. It's estimated that more than half of adults have been infected with CMV by age 40, according to the Centers for Disease Control and Prevention.

An antiviral drug does exist to treat CMV patients — Ganciclovir — but some can build a resistance to it and the drug can also cause kidney problems.

Weller spent decades researching treatments for the more well-known genital herpes virus, but she shifted gears recently at the urging of a fledgling state-backed program called PITCH (Program in Innovative Therapeutics), launched by Yale and UConn to facilitate collaboration among researchers and venture capitalists and to speed promising drug compounds into the commercial pipeline.

“We consider [CMV] as having a larger unmet clinical need,” Weller said in a recent interview.

She and her team are targeting a particular protein that is believed to be essential for CMV to replicate itself. The goal is to find a natural or synthetic compound that can restrain the protein and prevent dormant CMV infections from reactivating.

Weller is working with Yale's Center for Molecular Discovery because the school has a large library of drug molecules and enough capacity to work on multiple projects.

Last month, researchers at that lab began running a series of tests on Weller's targeted protein using high-end equipment in a process called “high throughput screening.”

At the conclusion of their work, Yale researchers will tell Weller which compounds reacted with the targeted protein.

The screening services provided by Yale aren't cheap. Weller would have had to seek funding to pay for them if it weren't for PITCH, which received $10 million in late 2015 from the Connecticut Bioscience Fund, administered by Connecticut Innovations.

The technology originated at pharmaceutical companies and started becoming more common in higher education 20 years ago.

Market potential

While Yale could vastly narrow down the list of potential promising compounds, their findings won't be quite ready for prime time.

From there the work will shift back to UConn, where Dennis Wright, a professor of medicinal chemistry and co-founder of PITCH, will assess the compounds and tweak their structures with the aim of making them more potent drug candidates.

“It's about starting to put together a package of data that would make a compelling case to investors looking for an early stage opportunity,” Wright said.

Weller has already formed a company called Quercus. Her younger brother Brad Weller, an attorney who has worked for public companies, is CEO.

Should her research progress far enough, Quercus would license the intellectual property from UConn. If she gets an antiviral drug to market, Connecticut Innovations would receive royalty payments for its investment. There are several big pharmaceutical companies in phase 3 trials for CMV drugs, though they are targeting different proteins, Weller said.

Because CMV is a more complex strain of the herpes virus, Weller is hoping that whatever she develops might also be effective against other, simpler forms.

She likens members of the virus to cars. They all have the same core parts, but some, like CMV, have added features.

“It's got a sunroof and a retractable antenna,” she said.

That makes CMV harder to work with, but offers a potentially more promising payoff.

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