New study on Hepatitis C drug treatment in vivo and in vitro

Hepatitis C virus (HCV) infection affects about 4.1 million in the United States and is the primary cause of liver cirrhosis and liver cancer. Current therapy against HCV is suboptimal. Daclatasvir, a direct acting antiviral (DAA) agent in development for the treatment of HCV, targets one of the HCV proteins (i.e., NS5A) and causes the fastest viral decline (within 12 hours of treatment) ever seen with anti-HCV drugs. An interdisciplinary effort by mathematical modelers, clinicians and molecular virologists has revealed that daclatasvir has two main modes of action against HCV and also yields a new, more accurate estimate of the HCV half-life.

Results of the NS5A study were published in the prestigious Proceedings of the National Academy of Sciences (PNAS) on February 18th, 2013.

"Ultimately, our study will help design better DAA drug cocktails to treat HCV," said Loyola University Health System (LUHS) and Stritch School of Medicine (SSOM) mathematical modeler Harel Dahari, Ph.D, who co-led the study. Dahari is one of five members of the Division of Hepatology at Loyola headed by Scott Cotler, MD who authored the study along with Thomas Layden, MD, HCV virologist Susan L. Uprichard, Ph.D and Dr. Uprichard's Ph.D graduate student Natasha Sansone. The study was co-led with Dr. Jeremie Guedj (Institut National de la Santé et de la Recherche Médicale), and conducted with Drs. Alan Perelson (Senior Fellow at Los Alamos National Laboratory), Libin Rong (Oakland University) and Richard Nettles (Bristol-Myers Squibb).

The new study documents HCV kinetic modeling during treatment both in patients and in cell culture that provides insight into the modes of action of daclatasvir. In addition, the study suggests a more accurate estimate of HCV clearance from circulation previously estimated in 1998 by Drs. Dahari, Layden, Perelson and colleagues in Science.

"Our modeling of viral kinetics in treated patients predicts that daclatasvir not only blocks the synthesis of the viral RNA within infected cells but also blocks the secretion of infectious virus from the cells," explained Dahari. This prediction was confirmed in Dr. Uprichard's laboratory using cultured liver cells that support the entire life cycle of HCV infection. Drs. Dahari and Uprichard are directors of a new program for experimental and translational modeling recently established at Loyola to promote the type of interdisciplinary research exemplified in this publication.

Additional 2013 Dahari Research Papers
Additional research conducted by Dahari and colleagues related to the new Loyola program for experimental and translational modeling are in press for publication in other professional journals:

  • A study on the effect of ribavirin on HCV kinetics and liver gene expression, led by researchers from the National Institute of Health and published in Gut.
  • A letter on understanding triphasic HCV decline during treatment in the era of IL28B polymorphisms and direct acting antiviral agents via mathematical modeling, published in the Journal of Hepatology.
  • A study showcasing a mathematical model of the acute and chronic phases of Theiler murine encephalomyelitis virus (TMEV) infection that can serve as an important tool in understanding TMEV infectious mechanisms and may prove useful in evaluating antivirals and/or therapeutic modalities to prevent or inhibit demyelination multiple sclerosis, published in the Journal of Virology.

Dr Dahari is a recognized international leader in the field of viral kinetics. "Loyola is honored to have Dr. Dahari as a member of the Hepatology faculty; his ground-breaking research will help reinforce Loyola's leadership in the treatment of hepatitis C," said David Hecht, MD, interim senior vice president, Clinical Affairs at LUHS and Chair of Internal Medicine in the SSOM.

Loyola University Health System has expanded hepatology services with physicians now available in Moline, Peoria, Rockford, Burr Ridge, Park Ridge, Homer Glen and Maywood, as well as in the Dearborn Station building in the South Loop and in Chicago's Chinatown neighborhood.

Most Popular Now

Top 20 breaking World Pharma News of 2017

We are proud to announce the top 20 most popular breaking World Pharma News from 2017. Have a wonderful 2018 new(s) year filled with health, happiness, and spectacular su...

Novartis advances head-to-head superiority trials …

Novartis announced today the initiation of SURPASS, a head-to-head clinical trial of Cosentyx® (secukinumab) versus proposed biosimilar adalimumab** in ankylosing spondyl...

New research paper shows that AstraZeneca has achi…

In a research paper published today by Nature Reviews Drug Discovery(1), AstraZeneca's IMED Biotech Unit documents a more than four-fold improvement in R&D productivity f...

Diabetes drug 'significantly reverses memory loss…

A drug developed for diabetes could be used to treat Alzheimer's after scientists found it "significantly reversed memory loss" in mice through a triple method of action...

Sandoz regulatory submission for proposed biosimil…

Sandoz, a Novartis division and the global leader in biosimilar medicines, announced today that the US Food and Drug Administration (FDA) has accepted its Biologics Licen...

Zika remains a research and public health challeng…

Since 2016, when Zika was declared by the World Health Organization as a public health emergency of international concern, the virus has become established in more than 8...

Dirt-dwelling microbe produces potential anti-mela…

A type of soil-dwelling bacterium produces molecules that induce death in melanoma cells, research at Oregon State University shows. The molecule is a secondary metabolit...

Try exercise to improve memory, thinking

For patients with mild cognitive impairment, don't be surprised if your health care provider prescribes exercise rather than medication. A new guideline for medical pract...

FDA approves first treatment for breast cancer wit…

The U.S. Food and Drug Administration today expanded the approved use of Lynparza (olaparib tablets) to include the treatment of patients with certain types of breast can...

Novartis Kisqali® received FDA Breakthrough Therap…

Novartis today announced Kisqali® (ribociclib) received US Food and Drug Administration (FDA) Breakthrough Therapy designation for initial endocrine-based treatment of pr...

Novartis appoints Elizabeth Barrett as Oncology He…

Novartis announced today that Elizabeth (Liz) Barrett, currently Global President Oncology at Pfizer, Inc., has been appointed CEO Novartis Oncology and a member of the E...

Berry gives boost to cervical cancer therapy

According to the Centers for Disease Control and Prevention, approximately 12,000 women in the United States are diagnosed with cervical cancer each year. One of the most...

Pharmaceutical Companies

[ A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Z ]