New Hep C Treatment with no Sides
C
I like it! I hope I live long enough to take advantage of it.
C
Cactus Jammies
"C" <nospa...@please.com.invalid> wrote in message
news:hfas61$a2d$1...@aioe.org...
> http://www.latimes.com/news/nationworld/nation/la-sci-hepatitis-c4-2009dec04,0,1848983.story
>
> I like it! I hope I live long enough to take advantage of it.
>
> C
ooops... read between the stars....
from:
http://www.webmd.com/hepatitis/news/20091203/liver-targeted-drug-stops-hepatitis-c
Liver-Targeted Drug Stops Hepatitis C
Durable DNA Molecule Blocks Hepatitis C Virus in Chimp Study
By Daniel J. DeNoon
WebMD Health NewsReviewed by Louise Chang, MDDec. 3, 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. (article quoted in full, below)
http://sciencenow.sciencemag.org/cgi/content/full/2009/1203/1
RNA Silencer Shows Promise for Hepatitis C
By Martin Enserink
ScienceNOW Daily News
3 December 2009
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-? 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 H�rsholm, 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
�rum, 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.
�rum 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
C
>
> "C" <nospa...@please.com.invalid> wrote in message
> news:hfas61$a2d$1...@aioe.org...
>> http://www.latimes.com/news/nationworld/nation/la-sci-hepatitis-c4-2009dec04,0,1848983.story
>>
>>
>> I like it! I hope I live long enough to take advantage of it.
>>
>> C
> ////////////////////////////////////////////////
>
> ooops... read between the stars....
Shit.
C