Athens, Ga. – For the estimated millions of AIDS patients
worldwide who are resistant or are developing resistance to currently available
medicines, a discovery by a University of Georgia researcher may offer a new treatment
option by targeting a previously elusive enzyme in the complex retrovirus
responsible for the devastating disease.
Approximately 40
million people worldwide have the infectious viral disease known as HIV-AIDS. Although
the number of drug-resistant patients is extremely difficult to estimate,
resistance to AIDS medications is widely viewed as a major global public health
problem.
A series of HIV
integrase inhibitors discovered by Vasu Nair, Georgia Research Alliance Eminent
Scholar in Drug Discovery at the University
of Georgia, recently was licensed by Georgia biotechnology company Inhibitex from the
University of Georgia Research Foundation. The license
included upfront license fees and shares of the company’s common stock, as well
as future milestone payments and royalties.
Inhibitex has
also agreed to provide significant research funding to support continued
research and development activity related to the licensed patents and for drug
discovery of new agents to treat patients infected with the hepatitis C virus
(HCV). Co-infection by HCV and other viruses is a problem commonly encountered by
HIV-AIDS patients.
HIV relies on
the activity of three key enzymes to survive and proliferate in the body:
reverse transcriptase, protease and integrase. While effective combinations of
HIV drugs attack the first two enzymes to stop replication, no fully approved
drugs stop the action of the HIV integrase enzyme, the insertion of HIV DNA
into human DNA. Nair calls this step in replication “the most devastating” in
HIV’s attack on human cells. Because
there is no human enzyme counterpart of HIV integrase, it is a particularly
significant and attractive disease target in the HIV replication cycle for
intervention by therapeutic agents.
In addition, for
many AIDS patients, the long-term regimens of anti-HIV drugs prove toxic, and
ultimately, their benefits decline. “HIV’s ability to rapidly mutate means that
patients usually develop resistance to their treatments over time,” explained
Nair.
Now, with HIV integrase
inhibitors, “we have a new class of drugs for people that is expected to
alleviate some of the problems associated with resistance and provide new treatment
options,” said Nair.
“Integrase
inhibitors are creating excitement in the pharmaceutical industry, scientific
community and for patients,” said Sohail Malik, director of technology
commercialization for UGARF. Merck & Co. recently reported favorable Phase
III clinical trials of Isentress, an experimental integrase inhibitor, and an independent
advisory committee recommended approval. The U.S. Food and Drug Administration
is currently reviewing the drug’s safety and effectiveness, and approval is
expected this month.
Drug developers
have been targeting HIV integrase for years, but without much success. Nair’s own
discovery had its beginning in NIH-funded work as far back as 1994, while he
was a researcher at the University
of Iowa. But, he said of
his early research, “those compounds didn’t sufficiently inhibit HIV
replication in infected cells.”
It wasn’t until
2002 when he came to the College of Pharmacy at the University of Georgia
that he began working on an entirely new class of HIV integrase inhibitors with
further NIH research support and had a major breakthrough. All told, Nair, who
directs UGA’s interdisciplinary Center for Drug Discovery, has worked for over
a decade to bring HIV integrase inhibitors to the point where they could be
licensed, an important milestone in the drug discovery, development and
approval process.
Because a patent
lasts just 20 years from the date it’s filed, and further development and
clinical trials take a number of years and significant investment, technology
commercialization offices like UGARF’s must work quickly to seek industrial
partners for commercialization.
“The license
agreement with Inhibitex is a good example of successful implementation of a fast
and efficient commercialization plan,” said Malik. The first patent on the
technology was filed in 2005, and the license agreement with Inhibitex was
signed in 2007.
Nair believes the
application of his discovery to halt HIV replication may just be the beginning
for the integrase inhibitor compounds. “The basic concepts of this discovery
have potential applications for one or more viral diseases caused by other infectious
RNA and DNA viruses,” he said.
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Note to editors: A downloadable photo of Vasu Nair is
available at http://www.ugaphoto.alumni.uga.edu/news/23060-022.jpg.
