Tuesday, 15 December 2009

Goods News About Hepatitis C

It seems there’s good news everywhere in the fight against Hep C. Firstly, the US congress has voted to lift the federal ban on funding syringe exchange programs after 21 years. Secondly, there has been some major breakthroughs for scientists in their search for an effective Hep C treatment. Two Australian researchers are responsible for one of the discoveries.

AIDS Activists Cheer End to Ban on Needle Exchange Funding
By Susan Sharon

After two decades, Congress has voted to lift a ban on federal funding of needle exchange programs. AIDS activists are cheering the move, which they say legitimizes needle exchange as a weapon in the fight against HIV/AIDS.

For years, needle exchange programs in three dozen states have provided clean needles to intravenous drug users as a way to reduce the transmission of HIV/AIDS and Hepatitis C. But the programs have relied solely on state and local funding because of a longtime ban at the federal level, where some have regarded needle exchange as an incentive for drug addicts to continue to use.

"People have been afraid that this is going to conflict with some sort of zero tolerance policy," says Bill McColl, who is with the Washington D.C.-based advocacy group AIDS Action. He says the vote to lift the ban is a vote for science over outdated stereotypes.

"There are eight federal reports that show that syringe exchange will decrease HIV and Hepatitis," he says. "It doesn't increase substance abuse. You know, this is a real opportunity to do some serious outreach to a population that is often overlooked."

In some places, such as Maine, needle exchange rates have been on the rise. At the Eastern Maine AIDS Network, for example, about 4,000 dirty needles are swapped out for clean ones every month. Just three years ago, only 300 clean needles were given out monthly.

Observers credit a new director with effective outreach. But Maine has also had an increase in IV drug use. And Andrew Bossie of the Maine AIDS Alliance says that's why federal funding for needle exchange is so important -- as many as 12 percent of people being infected with HIV are getting infected by injecting drugs.

"So we're really very happy that the U.S. House and Senate have lifted this ban and that we're on our way to more sound policies that prevent the spread of HIV."

Though it's a rural state, Maine has four needle exchange programs which Bossie says are all facing funding problems. Around the country there are about 200. President Obama has previously expressed support for liftting the ban on federal funding of needle exchange as a way to reduce rates of infection.

And while his expected signing of the bill later this month won't guarantee programs get additional funding, activists say it could give more options to those affected by state and local budget cuts.

Liver-Targeted Drug Stops Hepatitis C
Durable DNA Molecule Blocks Hepatitis C Virus in Chimp Study
By Daniel J. DeNoon
WebMD Health News
Dec 2009

Hepatitis C virus can't get a grip on the livers of chimps treated with a new antisense DNA drug.

The drug, dubbed SPC3649, doesn't attack the hepatitis C virus (HCV) itself. Instead, it blocks the tiny RNA molecules in the liver -- microRNA-122 or miR-122 -- that the virus must use to make new copies of itself. HVC causes disease only when it can replicate to high liver concentrations.

HCV levels drop 350-fold in chimps treated with SPC3649, find Robert E. Lanford, PhD, of San Antonio's Southwest foundation for Biomedical Research and colleagues.

"The drug worked exceptionally well in treating HCV infections in chimpanzees," Lanford said in a news release. In an email to WebMD he said, "We were very excited with the outcome."

The researchers studied four chimps chronically infected with HCV genotype 1, the most common HCV strain in the Americas and Australia. It's also the most treatment-resistant HCV strain.

Two chimps got a low dose of SPC3649, and two got a high dose, given once a week for 12 weeks. The higher-dose treatment was remarkably effective in suppressing HCV. The lower dose showed a strong but lesser effect in one chimp, but not in the other.

As long as the animals stayed on the drug -- and for two weeks after treatment stopped -- HCV levels remained low. But after treatment ended, HCV levels eventually rebounded to pretreatment levels.

Treatment, however, made the virus much more sensitive to the antiviral effects of interferon. Interferon, combined with ribavirin, is the best current treatment for HCV, but only about half of people infected with genotype 1 HCV get long lasting control of the virus. It's hoped that SPC3649 could eventually be combined with interferon to give the virus a knockout punch.

SPC3649 targets miR-122 in the liver, where it plays a role in cholesterol metabolism. The only side effect seen in the chimps was a rather dramatic lowering of LDL (bad) cholesterol. In earlier studies with green monkeys, the drug had a stronger effect on HDL (good) cholesterol. That would not be a good thing if it happens in humans, but SPC3649 affects cholesterol differently in different primate species.

"I suspect that at some point lowering HDL too much would be a problem if you did not lower LDL at the same time," Lanford said in his email. "I do not suspect that this will be a limitation of this drug, but human clinical trial data are needed to address this issue."

That data is on the way. The drug's manufacturer, Santaris Pharma of Hoersholm, Denmark, has begun a phase 1 safety trial in HCV patients. Santaris funded the Lanford study and Santaris researchers contributed to the work.

Beyond HCV: LNA Drugs vs. Cancer, Inflammation, More
SPC3649 is actually a man-made strand of nucleotides, the building blocks of DNA and RNA. The drug is actually an antisense nucleotide, meaning that it is assembled in a way that makes it complementary to its RNA target.

Antisense nucleotides inactivate their targets. But normal nucleotides quickly break down in the bloodstream. SPC3649 uses a proprietary technology to lock it together so that it does not break down. Santaris calls this a "locked nucleic acid (LNA)-modified oligonucleotide."

The LNA technology is not unique to SPC3649. Santaris has used the technology to create LNA drugs for cancer, inflammatory diseases, metabolic diseases, and rare genetic disorders. These drugs are in various stages of preclinical and clinical development with various partner companies.

The Lanford study was published online in the Dec. 3 issue of Science Express.

Aussies Aid Hepatitis C 'Breakthrough'
Sep 2009

An Australian-led team of international medical researchers may have scored an important breakthrough in the treatment of hepatitis C.

The team, led by Sydney molecular geneticist David Booth and Sydney University hepatitis C expert Jacob George, has identified a variant in an interferon gene which links it to the treatment of the chronic hepatitis C virus (HVC).

The gene, known as IL28B, was found to encode an interferon "lambda" involved with the suppression of viruses, including HCV.

Interferons, or proteins inhibiting the replication of viruses, are identified through the use of letters from the Greek alphabet.

The researchers said the new study showed use of the interferon-lambda in treatment could benefit those people identified as best suited to receive it and spare others the cost and side effects of their current treatments.

Prof George said the current standard treatment procedure for chronic HCV was combined therapy with pegylated interferon-alpha and ribavirin for about 11 months.

"This treatment can have side effects and only about 40 to 50 per cent of individuals infected with HCV show a positive response to it," Prof George said.

"The current study renews interest in therapies which involve this type of interferon, and suggest that combined treatment with interferon-alpha and interferon-lambda may prove a more effective treatment."

Dr Booth, a molecular geneticist with Westmead Millennium Institute who is widely recognised for his work with multiple sclerosis and genes that cause autoimmune disease, said the same principles applied to hepatitis C infection as to MS.

"We inherit from our parents subtle differences in the make-up of our immune system that can make a major difference in susceptibility to disease or how we respond to treatment," he said.

"Finding each of the few genes that have such an impact gives science an edge in the eventual prevention or control of many of the major diseases of humankind."

He said the finding that inherited differences in the interferon lambda gene has such an impact on the treatment of Hep C provided a valuable new lead into beating "an infection of epidemic proportion worldwide".

Almost 300 million people are known to have been infected with hepatitis C, which is a leading cause of liver disease.

Results of the study into interferon IL28B were published on Sunday's Nature Genetics website.

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