NIH gives SLU $2.2 million to design a cure for Hepatitis B

December 14, 2015

ST. LOUIS-- With proof-of-principle in his pocket and a new $2.2 million grant from the National Institutes of Health (NIH), SLU scientist John Tavis, Ph.D., will take his 25 year mission to finally develop a cure for the hepatitis B virus into the next phase.

Tavis, who is professor of molecular microbiology and immunology at Saint Louis University, says his team has built a warhead that will kill the virus; now, it's time to design a cruise missile that will deliver the drug.

After exposure, the hepatitis B virus can linger, causing chronic infection in many people. Over time, the illness causes liver damage. While current treatments can suppress the virus, they cannot fully kill it, and it will return if treatments are stopped.

More than 350 million people are chronically infected with the hepatitis B virus. Of those infected, up to 1.2 million die from liver failure and liver cancer each year.

Because current treatments are costly, lifetime medications, scientists are keen to develop better options, likely in the form of combination therapies, to knock out the virus for good.

Tavis and his team have finished one stage of research and are moving on to another in their quest to design a new drug.

"We've achieved the first stage of the laboratory research. We've developed the warhead of a drug, the portion that does the actual activity that the drug is designed to do. We did this with a class of compounds called alpha hydroxyl tropolones.

"We have advanced beyond what is called 'target identification and validation'," Tavis said. "We found something to hit in the virus and proved that it is a good thing to hit. Then, we identified about 35 inhibitors. This tells us about the types of compounds needed to block the viral activity. This is the first step to drug development. Now, we're done with proof-of-principle part of the work.

"The inhibitors we found are the warhead of the drug, but this is only one portion of a drug. The next part is the delivery, which involves all kinds of things. We must design a molecule for minimal toxicity, that can be absorbed by the body and that can last long enough for therapeutic benefit. Then, we've got to package it so people can take it in a pill. Ideally, we'd like to avoid injectables, which are difficult for people to take.

"So, now we've got to design the package -- the cruise missile -- that will hold and deliver the warhead."

The recent NIH grant will allow Tavis, his key collaborators Ryan Murelli, Ph.D., of the City University of New York and Marvin Meyers, Ph.D., director of medicinal chemistry at SLU's Center for World Health and Medicine, and the rest of his team to take their promising findings a step closer toward drug development. This stage will focus on medicinal chemistry, testing the drug in repetitive cycles aimed at optimizing the drug and limiting toxicity.

"We need an inhibitor that is safe enough and good enough to give to people," Tavis said. "This is very hard work. While this new grant won't get us all the way there, if we are very successful we will get deep into the preclinical stage in preparation for clinical trials."

Tavis credits early support from the NIH and SLU, as well as the unique collaborations possible through partnership with SLU's Center for World Health and Medicine (CWHM) with allowing his work to progress.

"Drug design has not traditionally been done in academia," Tavis said. "The work is not always compatible with academic duties and it requires an interdisciplinary team. It can be difficult to organize the workflow. But, the Center for World Health and Medicine at SLU is a unique resource. It has enabled those of us in the basic sciences to advance our work."

Initial research funding for Tavis's work included seed grants that allowed him to gather enough data to publish early findings and attract NIH funding.

"This project is a result of 25 years of background studies in basic science funded by the NIH," he said. "And, the initial stages of the more recent work were generously supported by seed grants from SLU through the President's Research Fund. We also received funding from the "Friends of the Saint Louis University Liver Center" and from SLU Cancer Center, as well as Washington University's Institute of Clinical and Translational Sciences. All of those different organizations saw value in this work at an early stage, invested, and now we are seeing the payoff."

Read about the 19-year problem Tavis cracked that led to his scientific breakthrough in the search for a cure for hepatitis B here: http://www.slu.edu/rel-tavis-24.

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious diseases.

SLU's Center for World Health and Medicine is dedicated to the development of medicines to treat diseases that affect the world's poor and underserved populations. The center consists of a multidisciplinary team of former pharmaceutical company scientists with extensive translational research experience. They have the skills to discover and develop small molecule drugs, and they are experienced in advancing such agents into clinical trials.
-end-


Saint Louis University

Related Hepatitis Articles from Brightsurf:

Busting Up the Infection Cycle of Hepatitis B
Researchers at the University of Delaware have gained new understanding of the virus that causes hepatitis B and the ''spiky ball'' that encloses its genetic blueprint.

Liver cancer: Awareness of hepatitis D must be raised
Scientists from the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG) have studied the most serious consequence of chronic hepatitis: hepatocellular carcinoma.

Hepatitis B: New therapeutic approach may help to cure chronic hepatitis B infection
Researchers at Helmholtz Zentrum München, Technical University of Munich (TUM) and the German Center for Infection Research (DZIF) have developed a novel therapeutic approach to cure chronic hepatitis B.

Anti-hepatitis medicine surprises
A new effective treatment of hepatitis C not only combats the virus, but is also effective against potentially fatal complications such as reduced liver functioning and cirrhosis.

Nanotechnology delivers hepatitis B vaccine
X-ray imaging shows that nanostructured silica acts as a protective vehicle to deliver intact antigen to the intestine so that it can trigger an immune response.

Checkmate for hepatitis B viruses in the liver
Researchers at Helmholtz Zentrum München and the Technical University of Munich, working in collaboration with researchers at the University Medical Center Hamburg-Eppendorf and the University Hospital Heidelberg, have for the first time succeeded in conquering a chronic infection with the hepatitis B virus in a mouse model.

How common is Hepatitis C infection in each US state?
Hepatitis C virus infection is a major cause of illness and death in the United States and injection drug use is likely fueling many new cases.

New strains of hepatitis C found in Africa
The largest population study of hepatitis C in Africa has found three new strains of the virus circulating in the general population in sub-Saharan Africa.

High stability of the hepatitis B virus
At room temperature, hepatitis B viruses (HBV) remain contagious for several weeks and they are even able to withstand temperatures of four degrees centigrade over the span of nine months.

Findings could lead to treatment of hepatitis B
Researchers have gained new insights into the virus that causes hepatitis B -- a life-threatening and incurable infection that afflicts more than 250 million people worldwide.

Read More: Hepatitis News and Hepatitis Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.