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Home > Health >

NIH clinical trial to assess race as factor in treatment success

By Susan Williams

What makes a particular medical treatment work successfully in one patient, but not another? And to take the question further, why would it be more effective for one racial group than another? To answer this, at least in the treatment of the hepatitis C virus (HCV), experiments are being carried out in Milton Taylor's laboratory on the Bloomington campus of Indiana University.

Milton Taylor's laboratory on the IU Bloomington campus is one of four ancillary facilities—and the only one not located in a medical school—which will study viral resistance to antiviral therapy in the treatment of hepatitis C.


Photo by Paul Martens

Much of Taylor's work is done in collaboration with INGEN at the IU School of Medicine. The amount of data involved in the study is overwhelming and requires analysis that would not be possible without the help of INGEN statisticians and bioinformaticists.

According to Taylor, IU professor of molecular biology and a fellow of the Institute of Molecular Biology, the university will participate in a clinical trial recently announced by the National Institutes of Health to examine the differences between African American and Caucasian patient response rates to interferon/ribavirin, a combination of two antiviral substances used in the current optimal treatment of chronic HVC.

"In previous studies, the response rate to treatment in Caucasians was about 20 to 40 percent depending on the type of interferon used, but the response rate in African Americans was less than 5 percent," explained Taylor. "There is a growing body of evidence confirming this difference."

The new study, Viral Resistance to Antiviral Therapy of Chronic Hepatitis C (Virahep-C), is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and coordinated by the University of Pittsburgh Graduate School of Public Health Epidemiology Data Center.

Taylor's lab at IU is one of four ancillary labs involved in the project, the only one not located in a medical school. Eight clinical centers also will participate in the study, which will enroll 400 patients over a one-year period, 200 African Americans and 200 Caucasians.

Patients will undergo an extensive initial medical evaluation and return periodically during and following treatment. The goal will be to determine the differences in response from one group to another, and also to look at differences between those who do respond and those who do not in both races. IU and the other three ancillary labs will investigate what might cause those differences.

"Our job in this large project is to analyze gene expression following interferon treatment. In other words, we'll look at as many genes as are expressed at any one time following treatment," said Taylor.

In the past, researchers commonly looked at one gene in one experiment, but a new technology resulting from the Human Genome Project can present an array of samples. Referred to as DNA or gene array, this technology allows researchers to look at the changes in expression of a number of genes simultaneously.

"We are using DNA chips containing 22,000 genes, or spots, on arrays. This obviously is not all the genes of an individual, but most metabolic and physiological pathways are covered, which allows us to assess which of those may be activated. Preliminary results indicate that somewhere between 1,000-2,000 of them may be activated by interferon," he continued.

"Since we are using RNA isolated from the blood of patients before treatment and also from controls, we should get a picture of what genes, if any, are actually activated by hepatitis C virus."

Much of Taylor's work is done in collaboration with the Indiana Genomics Project (INGEN) at the IU School of Medicine. The amount of data involved in this study is overwhelming, said Taylor, and requires a great deal of analysis that would not be possible without the help of INGEN statisticians and bioinfor-maticists.

Taylor has worked in the area of interferon, a natural antiviral compound, for some time. Most of the work done in his lab, he said, looks at the molecular activity of interferons, and how it stops virus infection and inhibits the growth of cancerous cells. In addition to this study on how interferon works, or doesn't, with hepatitis C, Taylor has other grants to pursue possible markers in the diagnosis of breast and other cancers.

Administrative work on Virahep-C began last August, and Taylor expects the first patient samples to arrive soon.

"We will follow up patient samples before treatment, and at 24, 48 and possibly 72 hours, one week, two weeks and at other time points up to 48 weeks," explained Taylor. "We should get a complete picture of what is transpiring after treatment."

HCV has infected an estimated 3.9 million Americans, 2.7 million of them chronically, according to the National Center for Infectious Diseases. While the number of new infections each year has dropped from 240,000 during the 1980s to 40,000 in 1998, it is still a serious illness. Causing liver disease in about 70 percent of those chronically infected, hepatitis C is the leading indicator of liver transplant.

"We hope to be able to predict who will respond to treatment and who will not," said Taylor. "Interferon treatment is very expensive and there are many side effects. We also hope to learn more about interferon therapy in general, as well as with hepatitis C. In the future, it may be possible to decide after a few days whether it is worth continuing treatment."

Hepatitis what?


"Few of us would know HCV from KFC. Yet this potentially lethal virus is now four times as widespread as HIV, and few of the nation's 3 million to 4 million carriers have any idea they're infected. HCV, or hepatitis C virus, was not even discovered until 1988."—–from the April 22 cover stories of "Newsweek"

Read more about hepatitis C at this Newsweek Web site:
http://www.msnbc.com/news/737946.asp#BODY



 
 
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Publication date: May 10, 2002
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