Hepatitis C Treatment’s Side Effects Can Now Be Studied in the Lab
Hannah Ritzman (11 AM Micro) found this article on Science Daily about a new way antivirus treatments can be studied in the lab. As I noted to Hannah when she submitted this, both my wife and I went to graduate school with Prof. Cameron, who was a PhD student in Biochemistry when we were in school at Case Western Reserve University in Cleveland. He now holds the Paul Berg chair of Biochemistry up at Penn State; Paul Berg is a Nobel laureate in Chemistry, who also did his PhD work in Biochemistry at CWRU. Here is Hannah’s summary:
A research team led by Craig Cameron, the Paul Berg Professor of Biochemistry and Molecular Biology at Penn State University published in ScienceDaily on November 16, 2012 their recent findings. They found the adverse side effects of certain hepatitis C medications can be replicated and observed in Petri dishes and test tubes. This new method is hoped to help understand recent failures of hepatitis C antiviral drugs in patients in clinical trials and also assist in identifying medications that eliminate all adverse effects. The team hopes their findings may help develop safer and more-effective treatments for hepatitis C, as well as other pathogens such as SARS and West Nile virus.
The hepatitis C virus (HCV), affecting over 170,000,000 people worldwide, is the leading cause of liver disease. Though antiviral treatments are effective in many patients, they cause serious side effects in others. The medication mimics the virus’s genetic material, and also the genetic material of the patient. While the drug causes damage to the virus, it also has the ability to affect the patient’s own healthy tissues.
This research team has developed a method to reveal adverse side effects in the safety of a laboratory setting, rather than in clinical trials where patients may be placed at risk. This method involves anti-HCV medications and, in Petri dishes and test tubes, has shown these drugs affect functions within a cell’s mitochondria. The cellular mitochondria, a structure responsible for making energy (ATP), is affected by these compounds and is likely a reason why we see adverse effects. Cameron noted certain individuals have “sick” mitochondria, meaning some individuals are more sensitive to the mitochondrial side effects of antiviral drugs.
Antiviral drugs, including the ones used to treat HCV, affect normal, healthy mitochondria by slowing ATP output. A person with normal mitochondria will experience low degree ATP and mitochondrial effects; a person who is already predisposed to mitochondrial dysfunction will not be able to make enough ATP.
One of the foreseen problems with clinical trials is that a drug may show to be effective, but if even a small percentage of patients have side effects, the U.S. Food and Drug Administration is obligated to put the trial on hold or stop the trial altogether. This possibility makes drug companies reluctant to invest money in drug trials after an adverse event has been observed, even when the drugs could help millions of people. The researchers hope their methods eventually become part of the pre-clinical development process for antiviral drugs.
Cameron added the next step for his team is to identify the genes that make some individuals respond poorly to these particular antiviral treatments. Blood samples combined with a diverse patient group and new method to test for toxicity may help discover which individuals will respond well and which will experience mitochondrial reactions, based on genetic profiles. This is hoping to be used in order to personalize medicine, and open the door to pre-screen patients so those with mitochondrial diseases can be treated with different treatments from the beginning.