Fw: UT Southwestern News Release April 17, 2003

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Subject: UT Southwestern News Release April 17, 2003

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NEW DRUGS RESTORE IMMUNE RESPONSE

BLOCKED BY HEPATITIS C VIRUS IN HUMAN CELLS

DALLAS – April 17, 2003 – A new generation of drugs restores the immune

response blocked by the hepatitis C virus, reducing the virus to nearly

undetectable levels in a matter of days, according to researchers at UT

Southwestern Medical Center at Dallas and UT Medical Branch at Galveston.

" We found that the new protease inhibitors could actually prevent the virus

from blocking this immune response and basically restore the innate

antiviral response in human cells, " said Dr. Gale, assistant

professor of microbiology at UT Southwestern and senior author of the study,

published online today in Science Express. " Our conclusion is that these new

drugs will have a dual efficacy. "

Protease inhibitors, which are already undergoing clinical trials as

therapies to treat chronic hepatitis C infections, target the enzymatic

activity of the viral protease. Protease, an enzyme that can split a protein

into component peptides, is required to process viral proteins into their

functional forms.

" If you block the protease, it neutralizes the virus and restores the host

response to infection, allowing the cell to clear the virus naturally, " said

Gale. " That type of mechanism of the drug was completely unexpected. "

Hepatitis C virus, which is primarily transmitted by intravenous drug use,

blood transfusions or blood products, as well as through sexual contact,

affects 4 million people in the United States, making it the most common

blood-borne infection in the nation. Hepatitis C virus is the leading cause

of cirrhosis and liver cancer and accounts for more than 8,000 U.S. deaths

annually.

The purpose of the study was to determine why hepatitis C virus is so

persistent in human cells. Eighty-five percent of individuals exposed to the

virus develop chronic infections that are

unresponsive to therapy. Seventy percent of those with chronic infections

develop chronic liver disease, and nearly 3 percent with long-term

infections die of related illnesses, according to the Centers for Disease

Control and Prevention.

Gale and his colleagues discovered that the virus persists, in part, because

it blocks the innate immune response of infected cells.

" We believe that is a major reason why hepatitis C virus causes chronic

infection, " Gale said.

Two different protease inhibitor drugs are in different stages of clinical

trials. The drugs will likely be evaluated in more detail considering these

findings, Gale said.

" As opposed to just studying how much the drug knocks down the virus, now we

will evaluate how the drug impacts the host cell's response to the

infection, " he said.

Dr. Stanley Lemon, dean of medicine at UTMB and director of its National

Institutes of Health-funded hepatitis research center, noted that protease

inhibitors active against the AIDS virus have revolutionized the treatment

of that disease.

" These new findings with hepatitis C virus suggest that protease inhibitors

will become an important addition to existing interferon treatments for

hepatitis C and that they will have equal if not greater impact on the

treatment of this important form of liver disease, " he said.

The lead author of the study was Eileen Foy, a student in UT Southwestern's

Medical Scientist Training Program. Other authors from UT Southwestern were

Dr. Chunfu Wang, postdoctoral researcher in microbiology, and Rhea Sumpter

Jr., student research assistant in microbiology. Other UTMB contributors

were Dr. Kui Li and Dr. Masanori Ikeda, from the department of microbiology

and immunology.

The study was supported by the Nation Institute of Allergy and Infectious

Diseases and the Ellison Medical Foundation.

###

This news release is available on our World Wide Web home page at

http://www.utsouthwestern.edu/home_pages/news/

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