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http://www.hepb.org/pdf/2014_Hep_B_Foundation_Annual_Report.pdf
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Hepatitis B Foundation 2014 Annual Report
The next three years will be the “make-it” period for the Hepatitis B Foundation and its research arm, the
Baruch S. Blumberg Institute. We have imposed an ambitious timeline for results because we believe the opportunity is now, and the need is urgent.
Our world-class research institute—renamed in 2013 as the Baruch S. Blumberg Institute in honor
of our co-founder and Nobel Laureate Dr. Blumberg—is poised to significantly accelerate the pace of research. We have recruited a group of first class scientists to join us fulltime at the Blumberg
Institute in 2015.
Our new scientists, however, aren’t starting from zero. Indeed, they will have a head start since
we have been preparing and building toward this goal for more than two decades. And all of our
scientists have pledged to identify breakthrough therapies for hepatitis B in the next three years.
We want, and plan for, our discoveries to go from the lab into human use as quickly as possible.
We know that this will require drug development experts with pharmaceutical company experience and we have already made arrangements to create technology development partnerships. This means that our scientists can focus on pioneering discoveries and our partners can carry them all the way to the clinic.
Our hope for the next 5 to 10 years is simple—
that a complete cure is found, which will benefit everyone living with chronic hepatitis B worldwide.
We are ready to make a bold new push to truly make hepatitis B history.
New Ways to Treat Hepatitis B
Putting the STING in Hepatitis B:
Using an innovative assay developed in the labs of Drs. Guo and Chang, a new method of treating HBV was discovered. Our small molecule “Stimulator of Interferon Genes” (STING) is one of the most exciting leads in the field and shows
that in tissue culture all detectable viral gene products can be eliminated. This finding was confirmed in a small animal study, too. The STING approach has moved to the front of our research strategies and is one of the more innovative immunotherapeutic approaches.
Guoet al, Antimicrobial Agents & Chemotherapy, 2014.
HBsAg Inhibitors:
We have developed some of the only drugs that target the hepatitis B virus surface
antigen (HBsAg). HBsAg is essential for viral replication and may also help the virus avoid detection by the patient’s immune system. We have produced several
drugs that reduce the amount of HBsAg secreted by infected cells, in tissue culture. Animal results are ongoing, with as yet inconclusive data. But this is a
very promising treatment approach.
Cuconati et al, in preparation.
Capsid Inhibitors:
We have identified novel inhibitors of the virus capsid assembly process. The capsid is the protein shield that surrounds the viral DNA and is an essential protein. It may also play a role in regulating viral gene expression from its
covalently closed circular (ccc) DNA as well as immune evasion. Our new capsid inhibitors have been shown to be potent inhibitors of viral production in vitro (tissue culture) and may even have immune altering functions. One class of our compounds has been validated as active in animal studies, too.
Campagna et al, J Virology, 2013.
Inhibitors of cccDNA:
We have identified compounds that repress hepatitis B cccDNA (Liu et al, 2013, PLOS Pathogens) and there is great interest in their development. Some of these leads were found by testing our comprehensive natural products collection
(Cuconati et al, in preparation) , which was donated to the Blumberg Institute by Merck & Co. in 2011.
Seeing is Believing:
Our computational chemists have created models of the intact hepatitis B virus that are 3-D depictions of the genome surrounded in its protein capsid home. We are using these images to help produce more potent capsid inhibitors.
Kulp et al, in preparation.
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