Hepatitis C treatment's side effects can now be studied in the lab

November 16, 2012 by Katrina Voss in Diseases, Conditions, Syndromes

Hepatitis C treatment's side effects can now be studied in the lab

The adverse side effects of certain hepatitis C medications can now be replicated and observed in Petri dishes and test tubes, thanks to a research team led by a Penn State University scientist. The new method helps to understand recent failures of hepatitis C antiviral drugs in some patients in clinical trials, and it also could help to identify medications that eliminate all adverse effects. The team's findings, which will be published in the journal PLOS Pathogens, may help to pave the way toward the development of safer and more-effective treatments for hepatitis C, as well as other pathogens such as SARS and West Nile virus. This image is an illustration of a human cell during a normal viral infection. Credit: Craig Cameron lab

(Medical Xpress)—The adverse side effects of certain hepatitis C medications can now be replicated and observed in Petri dishes and test tubes, thanks to a research team led by Craig Cameron, the Paul Berg Professor of Biochemistry and Molecular Biology at Penn State University. "The new method not only will help us to understand the recent failures of hepatitis C antiviral drugs in some patients in clinical trials," said Cameron. "It also could help to identify medications that eliminate all adverse effects." The team's findings, published in the current issue of the journal PLOS Pathogens may help pave the way toward the development of safer and more-effective treatments for hepatitis C, as well as other pathogens such as SARS and West Nile virus.

First author Jamie Arnold, a research associate in Cameron's lab at Penn State, explained that the (HCV), which affects over 170,000,000 people worldwide, is the leading cause of and, although antiviral treatments are effective in many patients, they cause serious side effects in others. "Many for treating HCV are chemical analogs for the building blocks of RNA that are used to assemble new copies of the virus's genome, enabling it to replicate," he said. "These medications are close enough to the virus's natural building blocks that they get incorporated into the virus's genome. But they also are different in ways that lead to the virus's incomplete replication. The problem, however, is that the medication not only mimics the virus's genetic material, but also the of the patient. So, while the drug causes damage to the virus, it also may affect the patient's own healthy tissues."

Hepatitis C treatment's side effects can now be studied in the lab
Enlarge

The adverse side effects of certain hepatitis C medications can now be replicated and observed in Petri dishes and test tubes, thanks to a research team led by a Penn State University scientist. The new method helps to understand recent failures of hepatitis C antiviral drugs in some patients in clinical trials, and it also could help to identify medications that eliminate all adverse effects. The team's findings, which will be published in the journal PLOS Pathogens, may help to pave the way toward the development of safer and more-effective treatments for hepatitis C, as well as other pathogens such as SARS and West Nile virus. This image illustrates an antiviral drug causing adverse effects. The skull and crossbones represent the antiviral drug that gets into the viral RNA, but also into the healthy mitochondrial RNA, causing side effects and problems. Credit: Craig Cameron lab

A method to reveal these in the safety of a laboratory setting, rather than in where patients may be placed at risk, has been developed by the research team, which includes Cameron; Arnold; Suresh Sharma, a research associate in Cameron's lab; other scientists at Penn State; and researchers from other academic, government, and corporate labs. "We have taken anti-HCV medications and, in and test tubes, we have shown that these drugs affect functions within a cell's mitochondria," Cameron explained. "The cellular mitochondria —- a tiny structure known as 'the powerhouse of the cell' that is responsible for making energy known as ATP—is affected by these compounds and is likely a major reason why we see adverse effects." Cameron noted that scientists have known for some time that certain individuals have "sick" mitochondria. Such individuals are likely more sensitive to the mitochondrial side effects of antiviral drugs.

"We know that antiviral drugs, including the ones used to treat HCV, affect even normal, healthy mitochondria by slowing ATP output," Arnold added. "While a person with normal mitochondria will experience some ATP and mitochondrial effects, a person who is already predisposed to mitochondrial dysfunction will be pushed over the 'not enough cellular energy' threshold by the antiviral drug. The person's mitochondria simply won't be able to keep up."

Hepatitis C treatment's side effects can now be studied in the lab
Enlarge

The adverse side effects of certain hepatitis C medications can now be replicated and observed in Petri dishes and test tubes, thanks to a research team led by a Penn State University scientist. The new method helps to understand recent failures of hepatitis C antiviral drugs in some patients in clinical trials, and it also could help to identify medications that eliminate all adverse effects. The team's findings, which will be published in the journal PLOS Pathogens, may help to pave the way toward the development of safer and more-effective treatments for hepatitis C, as well as other pathogens such as SARS and West Nile virus. This image is an illustration of an antiviral drug without adverse effects. The ideal situation is to design a drug that would get into the viral RNA only, but not into the mitochondrial RNA. Credit: Craig Cameron lab

One of the problems with clinical trials, Arnold explained, is that a drug may be shown to be quite effective but, if even a miniscule 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 still help millions of people. The researchers hope that their methods eventually will become a part of the pre-clinical development process for this class of . "If we can show, in the lab, that a drug will cause side effects, then these compounds will not enter lengthy, expensive clinical trials and cause harm to patients " he said. "What's more, a drug company can invest its money more wisely and carefully in drug research that will produce safe and effective products. Better and more-willing investments by drug companies ultimately will help patients, because resources will be spent developing drugs that not only work, but that are safe for all patients."

Cameron added that the next step for his team is to identify the genes that make some individuals respond poorly to these particular antiviral treatments. "By taking blood samples from various patients and using the new method to test for toxicity in the different samples, we hope to discover which individuals will respond well and which will experience mitochondrial reactions, based on their genetic profiles," he said. "That is, we hope to use this method as a step toward truly personalized medicine, opening the door to pre-screening of patients so that those with mitochondrial diseases can be treated with different regimens from the start."

The team members also hope their method will be a means to study toxicity and in other diseases. "Specifically, our technology will illuminate toxicity of a particular class of compounds that interrupts viral RNA synthesis," Cameron said. "While this class of compounds currently is being developed for treatment of HCV, a wide range of other RNA viruses, including , Dengue virus, SARS coronavirus, and perhaps even the Ebola virus, could be treated using this class of compounds as well."

Journal reference: PLoS Pathogens search and more info website

Provided by Pennsylvania State University search and more info website

4.5 /5 (6 votes)  

Rank 4.5 /5 (6 votes)
Relevant PhysicsForums posts

More news stories

Swine flu pandemic of 2009 more deadly for younger adults, study finds

As the world prepares for what may be the next pandemic strain of influenza virus, in the H7N9 bird flu, a new UC Irvine study reveals that the 2009 H1N1 swine flu pandemic was deadliest for people under the age of 65, while ...

Diseases, Conditions, Syndromes created 13 hours ago | popularity not rated yet | comments 0

Polio cases found in Kenya and Somalia, WHO says

The World Health Organization says the Horn of Africa is experiencing an outbreak of polio with cases confirmed in Kenya and Somalia.

Diseases, Conditions, Syndromes created 14 hours ago | popularity not rated yet | comments 0

SARS-like virus claims new life in Saudi

A man who had contracted the coronavirus has died in Saudi Arabia, raising the death toll in the kingdom from the SARS-like virus to 17, the health ministry announced on its website on Wednesday.

Diseases, Conditions, Syndromes created 14 hours ago | popularity not rated yet | comments 0

Novel approach for influenza vaccination shows promise in early animal testing

A new approach for immunizing against influenza elicited a more potent immune response and broader protection than the currently licensed seasonal influenza vaccines when tested in mice and ferrets. The vaccine ...

Diseases, Conditions, Syndromes created 14 hours ago | popularity not rated yet | comments 0 | with audio podcast

Mild hypothyroidism raises mortality risk among heart failure patients

Patients with underlying heart failure are more likely to experience adverse outcomes from mild hypothyroidism, according to a recent study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & ...

Diseases, Conditions, Syndromes created 16 hours ago | popularity not rated yet | comments 0


Slowing the aging process—only with antibiotics

Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.

Researchers complete largest genetic sequencing study of human disease

Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.

Rate of bicycle-related fatalities significantly lower in states with helmet laws

Existing research shows that bicyclists who wear helmets have an 88 percent lower risk of brain injury, but researchers at Boston Children's Hospital found that simply having bicycle helmet laws in place showed a 20 percent ...

Brain can be trained in compassion, study shows

Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.

Having both migraines, depression may mean smaller brain

(HealthDay)—Migraines and depression can each cause a great deal of suffering, but new research indicates the combination of the two may be linked to something else entirely—a smaller brain.

Enzyme-activating antibodies revealed as marker for most severe form of rheumatoid arthritis

In a series of lab experiments designed to unravel the workings of a key enzyme widely considered a possible trigger of rheumatoid arthritis, researchers at Johns Hopkins have found that in the most severe ...