Posted on 12/05/2009 7:52:36 PM PST by neverdem
Researchers have come up with a completely new way to thwart hepatitis C: Go after the host, not the virus. Genetically silencing a small piece of RNA in chimpanzees effectively suppresses the hepatitis C virus (HCV), a new study shows--and the virus appears unable to become resistant to the treatment. But experts caution that the approach needs to be scrutinized carefully for side effects.
New drugs against HCV are badly needed. More than 170 million people worldwide have contracted the virus, which is transmitted primarily via injection drug use and through the transfusion of blood and blood products. The virus slowly scars the liver, leading to liver failure and sometimes liver cancer.
The standard treatment, a combination of two antiviral drugs called pegylated interferon-α and ribavirin, takes 24 to 48 weeks, can cause a range of side effects, and fully eliminates the virus in only 50% to 80% of patients. Pharmaceutical companies are developing several new antiviral drugs, including so-called polymerase and protease inhibitors, but the virus can become resistant to these quite easily.
The new study builds on a discovery published in Science in 2005 by Stanford University virologist Peter Sarnow and his colleagues. The team found that HCV depends on a tiny piece of RNA that is produced by the host and involved in the regulation of hundreds of genes, many of them related to cholesterol and lipid synthesis. Exactly what the "micro-RNA" snippet, called miR-122, does for the virus is still unclear; it may boost its replication or stability, or it may somehow protect it from the immune system.
Sarnow's work led Santaris Pharma, a biotech in Hørsholm, Denmark, to develop a candidate drug that can block miR-122. The compound, called SPC3649, is a short piece of artificial DNA that blocks miR-122 in mice and in green African monkeys. But those species don't get hepatitis C.
In the new paper, published online today in Science, the researchers tested the drug in four chimpanzees, the only nonhuman animal that gets HCV. The chimps had been infected with HCV in previous studies at the Southwest Foundation for Biomedical Research in San Antonio, Texas. Two of them were injected weekly with a low dose of SPC3649 for 12 weeks, the other two with a high dose.
The high dose reduces the amount of virus in the chimps' liver by more than 99.5%, the researchers found. (With the lower dose, one of the animals had a smaller decline, whereas the other responded poorly.) Needle biopsies from their livers, taken while the animals were anaesthetized and examined under a microscope, showed that the treatment resulted in more healthy-looking tissue. Throughout the study, there were no signs of resistance; the virus didn't rebound as the weeks passed--as often happens with other drugs--and there were no genetic changes in the place where the virus binds to miR-122. Targeting a host micro-RNA may be a smarter strategy than targeting a viral protein, says Santaris's Vice President and Chief Scientific Officer Henrik Ørum, because the virus cannot modify the host the way it can its own genes.
"It's a very nice proof of principle," says virologist Ben Berkhout of the Academic Medical Center in Amsterdam; the reduction in viral load is "very robust," he adds. Stanley Lemon of the University of Texas Medical Branch in Galveston, a co-author on Sarnow's 2005 paper, agrees. But he warns that with a drug that regulates the expression of so many genes--including some cancer-related ones--there are serious concerns about side effects. None were observed in the study, but still, "if I were leading a pharmaceutical company looking where to invest my money, I might be worried about that," says Lemon.
Ørum agrees that there is a risk, but he points out that hepatitis C is a life-threatening disease and that the hope is that patients would only have to take SPC3649 for a limited time, presumably with another drug, before they clear the virus. Santaris has completed a phase I study of the drug--in which safety is tested in healthy human volunteers--but the results have not been published.
Meanwhile, it's unclear whether the same strategy can have any use in other infections, says virologist Bryan Cullen of Duke University Medical Center in Durham, North Carolina, because currently no other virus is known to be dependent on a human microRNA. "I keep hearing rumors about other papers out there," says Cullen. "But for the moment, this is a unique case."
Related Site:
Therapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection
Could they apply this to Herpes?
Probably not since herpes is a retro virus.
Right.
Herpes is a DNA virus.
This may be the next level of treatment if DNA applications don’t do the trick. RNA is the “gatekeeper” and “on/off” switch for DNA.
My point was that herpes is not a retrovirus.
My brother died this past April from Hep C. from a tainted blood transfusion he recieved after surgery on his back in 1994.
Herpes is a family of viruses. One of the most troublesome/painful is herpes zoster known as shingles. A friend had an attack after he altered his diet and messed up his lysine/argenine ratio. I think he had stopped eating all dairy/milk products and shifted to nuts and brewers yeast. This is not to say that nuts and brewers yeast are bad for you, only that one needs to be careful with sudden diet shifts. At any rate, taking lysine tablets is a good idea if you feel a herpes attack coming on, whether cold sores or genital herpes. Incidentally, lysine and argenine are amino acids, found in meat, etc.
Very sorry about your brother. I have hep C from a blood transfusion as a teenager. I’ve had it a long time, 27 or more years. When I tried to give blood in 1982 I was told I had non A non B hep. There wasn’t a hep C yet.
interesting.
Thanks for your comforting thought. I miss him very much, he was my buddy.
The hospital contacted him two years later and told him that he had been infected with hep C. He was devastated. He couldn’t take Interferon because he had two little kids to support.
My brother is also dead from Hep C & MRSA, he was a drug addict . I didn’t find out for months so there was never a goodbye. When we were younger he was my buddy too. Prayers for both of our brothers.
“He couldn’t take Interferon because he had two little kids to support.”
Some people can take it and some can’t. I took it and worked every day but thank God I was able to work from home. It still almost ended my marriage as I became a short-tempered monster from being so sick.
I'm so sorry to hear that, we never had a chance to say goodbye, but four days before he died we had a wonderful day together.
Prayers for both of our brothers.
Thanks for the prayers, I pray for him every night, I'll surely add your brother to them.
He was a High Rise Construction Boss and knew it would be too dangerous to be on the top of a 20 or 30 story building while he was sick and weak.
Glad to hear your marriage made it.
“He was a High Rise Construction Boss and knew it would be too dangerous to be on the top of a 20 or 30 story building while he was sick and weak.”
There’s no way he could have done that. I couldn’t even walk the dog around the block I was so sick. My Doctor told me of people who had very few side effects from the treatment.
I wish you all the best.
Thank you.
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