March 19, 2012

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March 19, 2012 in Medical research

Chemists at the University of California, San Diego have produced the first high resolution structure of a molecule that when attached to the genetic material of the hepatitis C virus prevents it from reproducing.

Hepatitis C is a chronic infectious disease that affects some 170 million people worldwide and causes chronic liver disease and liver cancer. According to the Centers for Disease Control and Prevention, hepatitis C now kills more Americans each year than HIV.

The structure of the molecule, which was published in a paper in this week's early online edition of the journal Proceedings of the National Academy of Sciences, provides a detailed blueprint for the design of drugs that can inhibit the replication of the hepatitis C virus, which proliferates by hijacking the cellular machinery in humans to manufacture duplicate viral particles.

Finding a way to stop that process could effectively treat viral infections of hepatitis C, for which no vaccine is currently available. But until now scientists have identified few inhibiting compounds that directly act on the virus's ribonucleic acid (RNA) genome—the organism's full complement of genetic material.

"This lack of detailed information on how inhibitors lock onto the viral genome target has hampered the development of better drugs," said Thomas Hermann, an associate professor of chemistry and biochemistry at UC San Diego who headed the research team, which also included scientists from San Diego State University. The team detailed the structure of a molecule that induces the viral RNA to open up a portion of its hinge-like structure and encapsulate the inhibitor like a perfectly fit glove, blocking the ability of the hepatitis C virus to replicate.

The molecule is from a class of compounds called benzimidazoles, known to stop the production of viral proteins in infected human cells. Its three-dimensional atomic structure was determined by X-ray crystallography, a method of mapping the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread. The angles and intensities of the light beams allowed the scientists to calculate the structure of the viral RNA-inhibitor complex.

"This structure will guide approaches to rationally design better drug candidates and improve the known benzimidazole inhibitors," said Hermann. "Also, the crystal structure demonstrates that the binding pocket for the inhibitors in the hepatitis C virus RNA resembles drug-binding pockets in proteins. This is important to help overcome the notion that RNA targets are so unlike traditional protein targets that drug discovery approaches with small molecule inhibitors are difficult to achieve for RNA."

Provided by University of California - San Diego (news : web)

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877-HELP-4-HEP; a Peer Advocacy Success Story

San Francisco, CA, March 19, 2012 --(PR.com)-- The first week of February brought both good news and bad news to Mary*. She learned that her husband was an early responder to the powerful triple drug cocktail for hepatitis C. She also found out that their family’s state-sponsored health insurance coverage was going to be terminated.

Several months ago, Mary had called 877-HELP-4-HEP (877-435-7443). Many conversations with peer counselors helped her husband prepare to start treatment at the beginning of the year and provided much needed emotional support for the family.

One counseling conversation raised a flag. A few short weeks after her husband started treatment; Mary mentioned that she got a part-time job to help buy groceries for their family of five. Her HELP-4-HEP counselor was on the alert. What Mary did not consider was that her extra wages might alter her family eligibility for state-sponsored insurance at a very inopportune time.

Mary’s counseling team began reviewing options to avoid disruptions to treatment. When her “bad news” came, it was met with an action plan. Mary’s husband will continue under the care of his current treating physician, receive medications at no cost through patient assistance programs, and get the tests necessary to monitor his progress at a discount.

“This story could have had another ending. It was the proactive work of a group of HELP-4-HEP counselors who made the difference for this family,” said peer counselor, Sue Simon from Hepatitis C Association.

HELP-4-HEP is a project of The Support Partnership which includes HealthPro (formerly Hep-C ALERT), FL; Hepatitis C Association, NJ; Hepatitis Education Project, WA; Hep C Connection, CO; and Project Inform, CA. The helpline operates Monday through Friday, 9:00am to 7:00pm EST. To learn more, visit www.help4hep.org  or email info@help4hep.org.

877-HELP-4-HEP peer counselors are available to help your patients too. Palm cards are now available to distribute. Please email your organization’s contact name, site name, address, phone number, and the number of cards desired.

* Name changed.

Contact Information

The Support Partnership
Andi Thomas
954-692-0450
Contact
www.help4hep.org
Denny Simon
908-812-2488

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Hep C Death Rates Steadily Increase

hepatitisc_250

Monday, March 19, 2012

Researchers recently uncovered some startling news concerning hepatitis C: death rates from the virus gradually increased from 1999 to 2007 and now exceed HIV-related deaths in the United States.

The study, primarily funded by the Centers for Disease Control and Prevention, was recently published in the Annals of Internal Medicine.

According to the study, an estimated 3.2 million people in this country are infected with chronic hepatitis C virus. At least half of those infected may not even know it.

Researchers analyzed death records for 22 million people from 1999 to 2007 to examine mortality rates for hepatitis B, hepatitis C and HIV (to use for comparison). They found that over the course of eight years, annual deaths from hepatitis C increased (15,106 in 2007), while those from HIV decreased (12,734 in 2007).

Baby boomers seem to be affected the most. One in every 33 is infected with the virus.

The current screening guidelines from the CDC only recommend testing people known to be at high risk. Now the agency is debating whether to change those guidelines to encourage anyone born between 1945 and 1965 to get a one-time screening. The one-time screening, according to the CDC, has the potential to save 82,000 lives.

For more information about the study, visit www.annals.org.

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POSTED: MARCH 19, 2012

by George Ochoa

A preventive vaccine against hepatitis C virus (HCV) that would potentially be the first in that class is entering a Phase I/II clinical trial, according to the Basel, Switzerland-based biopharmaceutical company Okairos.

This is the first multicenter, double-blinded, randomized, placebo-controlled trial of a vaccine to prevent HCV infection, the company stated. The trial, born of collaboration between Okairos and the National Institute of Allergy and Infectious Diseases, will be conducted by co-principal investigators from Johns Hopkins University and the University of California, San Francisco.

The Phase I/II trial follows promising Phase I results published in January in Science Translational Medicine (Barnes et al. 2012;4:115ra1). In that study in healthy volunteers, the T-cell–based preventive vaccine was safe and well tolerated, and, the authors reported, it was shown possible “to generate very strong, broad, long-lasting, and functional T-cell responses against HCV in healthy donors using an adenovirus-based approach.” The Phase I/II trial will test the vaccine’s potential effectiveness in protecting against chronic HCV infection.

Enrolling 350 subjects, the trial will begin with an interim Phase I analysis of safety and immunogenicity data in a subset of the participants. The study’s primary endpoints will measure the incidence of chronic HCV infection, and the vaccine’s safety and tolerability.

Okairos’ HCV vaccine is based on a technology platform that uses proprietary, chimpanzee-derived adenovirus vectors to stimulate a robust T-cell response against selected antigens. Okairos plans to develop other T-cell vaccines against infectious diseases for which there are currently no effective vaccines, and to pursue therapeutic vaccines to treat cancer.

—Based on an Okairos press release and the article in Science Translational Medicine

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Also See: Okairos Announces Initiation of Phase I/II Clinical Trial for Potential First-in-Class Hepatitis C Vaccine

Antiviral strategies in hepatitis C virus infection

Journal of Hepatology
Volume 56, Supplement 1 , Pages S88-S100, 2012

Christoph Sarrazin, Christophe Hézode, Stefan Zeuzem, Jean-Michel Pawlotsk

Abstract

Summary

Resolution of the three-dimensional structures of several hepatitis C virus (HCV) proteins, together with the development of replicative cell culture systems, has led to the identification of a number of potential targets for direct-acting antiviral (DAA) agents. Numerous families of drugs that potently inhibit the HCV lifecycle in vitro have been identified, and some of these molecules have reached early to late clinical development. Two NS3/4A protease inhibitors, telaprevir and boceprevir, were approved in Europe and the United States in 2011 in combination with pegylated interferon (IFN)-α and ribavirin for the treatment of chronic hepatitis C related to HCV genotype 1, in both treatment-naïve and treatment-experienced patients. Sustained virological response rates in the range of 6675% and 5966% (2988% if the response to the first course of therapy is taken into account) have been achieved in these two patient populations, respectively, with treatment durations of 24 to 48 weeks. A number of other DAAs are at the clinical developmental stage in combination with pegylated IFN-α and ribavirin or with other DAAs in IFN-free regimens, with or without ribavirin. They include second-wave, first-generation, and second-generation NS3/4A protease inhibitors, nucleoside/nucleotide analogue inhibitors and non-nucleoside inhibitorsof HCVRNA-dependent RNA polymerase, inhibitors of nonstructural protein 5A (NS5A) and host-targeted compounds, such as cyclophilin inhibitors and silibinin. The proof of concept that IFN-free regimens may lead to HCV eradication has recently been brought. However, new drugs may be associated with troublesome side effects and drugdrug interactions, and the ideal IFN-free DAA combination remains to be found.

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