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

FDA approves Roche's OCREVUS™ (ocrelizumab) for re…

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the US Food and Drug Administration (FDA) approved OCREVUS™ (ocrelizumab) as the first and only medicine for both ...

Read more

First collaborative definition of patient centrici…

AstraZeneca announced that BMJ Innovations has published the first collaborative definition of patient centricity for the pharmaceutical industry. The definition was co-d...

Read more

High doses of vitamin C to improve cancer treatmen…

Clinical trials found that it is safe to regularly infuse brain and lung cancer patients with 800 - 1000 times the daily recommended amount of vitamin C as a potential st...

Read more

Deep learning algorithm could boost drug developme…

Artificially intelligent algorithms can learn to identify amazingly subtle information, enabling them to distinguish between people in photos or to screen medical images ...

Read more

Bristol-Myers Squibb enters into separate agreemen…

Bristol-Myers Squibb Company (NYSE:BMY) today announced that it has entered into two separate agreements to license BMS-986168, an anti-eTau compound in development for ...

Read more

Tagrisso (osimertinib) receives US FDA full approv…

AstraZeneca today announced that the US Food and Drug Administration (FDA) has granted full approval for Tagrisso (osimertinib) 80mg once-daily tablets, for the treatment...

Read more

A one-two punch hits pancreatic cancer where it hu…

Australian scientists have uncovered a promising new approach to treating pancreatic cancer, by targeting the tissue around the tumour to make it 'softer' and more respon...

Read more

FDA allows marketing of first direct-to-consumer t…

The U.S. Food and Drug Administration today allowed marketing of 23andMe Personal Genome Service Genetic Health Risk (GHR) tests for 10 diseases or conditions. These are ...

Read more

Novartis to strengthen R&D pipeline by in-lice…

Novartis has exercised an option to in-license ECF843 for ophthalmic indications worldwide (outside Europe). The closing of the deal is subject to customary closing condi...

Read more

New drug delivery system shows promise for fightin…

A new cancer-drug delivery system shows the ability to exploit the oxygen-poor areas of solid tumors that make the growths resistant to standard chemotherapy and radiatio...

Read more

Towards a safe and scalable cell therapy for type …

More than 36 million people globally are affected by type 1 diabetes (T1D), a lifelong disorder where insulin producing cells are attacked and destroyed by the immune sys...

Read more

XELJANZ® (tofacitinib citrate) receives marketing …

Pfizer Inc. (NYSE:PFE) announced today that the European Commission (EC) has approved XELJANZ® (tofacitinib citrate) 5 mg twice daily (BID) oral tablets in combination wi...

Read more

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 ]