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Hepatitis B cure sought with help of animal research

OHSU has created nonhuman primate model for virus that has infected 2 billion worldwide
Ben Burwitz, a white male in a lab coat, with two female colleagues, Lauren Rust and Sreya Biswas, looking at a computer monitor on a desk in a medical lab.
Benjamin Burwitz, Ph.D., works with fellow OHSU researchers Sreya Biswas, Ph.D., (left) and Lauren Rust, Ph.D. (right). Burwitz led the development of a nonhuman primate model for hepatitis B. (OHSU/Kristyna Wentz-Graff)

Oregon Health & Science University’s nonhuman primate model of hepatitis B is about to help biotechnology and pharmaceutical companies develop new treatments that seek to cure the millions of people living with chronic hepatitis B.

Headshot of Ben Burwitz, Ph.D., a smiling white male.
Benjamin Burwitz, Ph.D. (OHSU/Kristyna Wentz-Graff)

“While it may not grab much of the public’s attention, there are more people living on this planet with hepatitis B than HIV,” said Benjamin Burwitz, Ph.D., an assistant professor at the OHSU Vaccine and Gene Therapy Institute and an affiliate assistant professor at the OHSU Oregon National Primate Research Center, who led the model’s development. “I hope our rhesus macaque model will lead to new treatments that can alleviate those suffering from chronic Hepatitis B.”

Even though a vaccine has been available since the 1980s, about 2 billion people worldwide have been infected with the hepatitis B virus. The vaccine doesn’t work for about 10% of those who receive it, and it requires cold storage, which makes bringing the vaccine to remote areas challenging.

Those who are infected as children usually develop chronic hepatitis B, which can cause fatigue, nausea, jaundice, cirrhosis and liver cancer, and can even make a liver transplant necessary. About 257 million people worldwide and 862,000 Americans are living with chronic hepatitis B.

Other animal models for hepatitis B exist, including a humanized liver model in mice developed by OHSU’s Markus Grompe, M.D., in 2007, but nonhuman primates are typically preferred to model human disease because they more closely resemble our anatomy and immune system. The new model in rhesus macaques was first published in Nature Communications in 2017.

Ben Burwitz, Ph.D., smiling in his lab.
Benjamin Burwitz, Ph.D., led the development of a nonhuman primate model of hepatitis B, which has infected 2 billion people worldwide. OHSU is working with companies that are interested in using the model to evaluate potential new treatments for chronic hepatitis B. (OHSU/Kristyna Wentz-Graff)

The main class of drugs currently available to treat chronic hepatitis B are the same antiviral medications used to treat HIV. Antivirals prevent a virus from infecting new cells, but don’t prevent already infected cells from releasing antigens that trigger liver inflammation, which can cause hepatitis B symptoms. Antiviral drugs must be taken for life. Researchers are now seeking a medication that can be taken once, or for a short while, to cure hepatitis B.

Burwitz is working with companies that are interested in using OHSU’s model to evaluate new drugs they’re developing to treat hepatitis B.

One of those companies is Houston, Texas, biotechnology startup Stingray Therapeutics, which is developing a drug designed to boost immune responses. While their potential therapy was initially imagined to fight cancer, Stingray researchers realized similar immune processes are involved in counteracting both cancerous cells and the hepatitis B virus.

Lauren Rust, Ph.D. (left) and Sreya Biswas, Ph.D. (right) shown working in lab coats in Ben Burwitz's medical laboratory.
Lauren Rust, Ph.D., (left) and Sreya Biswas, Ph.D., work in the lab of OHSU researcher Benjamin Burwitz, Ph.D. Burwitz led the development of a nonhuman primate model for hepatitis B. Stingray hopes to begin and complete its first round of studies in the nonhuman primate model by the end of this year. (OHSU/Kristyna Wentz-Graff)

“Dr. Burwitz’s model is truly a remarkable and much-needed addition to HBV research tools,” said Stingray CEO and Co-Founder Jonathan Northrup, M.B.A. “There isn’t a better way to know whether our therapy could fight hepatitis B without testing it directly in people, which we don’t want to do before we can evaluate its safety through preclinical studies like this.”

Stingray hopes to begin and complete its first round of studies in the nonhuman primate model by the end of this year.

The National Institutes of Health (grant R01 AI157612) and Vir Biotechnology, Inc., (OHSU SRA-17-077) supported the development of OHSU’s nonhuman primate hepatitis B model.

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