News (Updated May 1,
2011)
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Use of chemical systems
biology may represent the future of drug discovery
Researchers at the
Nelfinivir is a protease
inhibitor that prevents replication of the HIV virus, but it has also been found
to have a positive effect on a number of solid tumor types, and is currently in
clinical trial as a cancer therapy. However, the mechanism of how the drug
worked in humans was not clear.
The researchers discovered
that Nelfinavir may interact with multiple human protein kinases – enzymes
that modify other proteins and regulate the majority of cellular pathways.
Protein kinases comprise approximately 2 percent of the human genome, and are
important anti-cancer drug targets.
Surprisingly, the
interactions between Nelfinavir and kinases are much weaker than those from more
specific, rationally designed drugs, said Philip Bourne, PhD, professor of
pharmacology at UC San Diego Skaggs School of Pharmacy and Pharmaceutical
Sciences. Bourne and colleagues suggest that it is the collective effect
of these weak interactions that leads to the clinical efficacy of Nelfinavir.
The research team – Li
Xie, PhD, from UC San Diego, Thomas Evangelidis, a former graduate student in
Bourne’s lab, now at the
While drug molecules are
designed to bind to targeted proteins in order to achieve a therapeutic effect,
small drug molecules can attach to off-target proteins with similar binding
sites. The result may be unwanted side effects or, as in the case of
Nelfinavir, a secondary and positive effect.
In the traditional
strategy for drug discovery, scientists use high-throughput screening to find a
suitable drug target. However, utilizing the RCSB Protein Data Bank – a
worldwide repository of tens of thousands of three-dimensional protein
structures – the UCSD researchers computationally compared binding sites in
order to identify which proteins might be unintended targets.
Taking a single drug
molecule, they looked at all proteins encoded by the human proteome to which
that molecule could possibly bind.
“Computer analysis
allows us to search for other binding sites that match a particular drug-binding
site – like looking for other locks that can be opened by the same key,”
said Lei Xie.
While this novel
computational pipeline is promising in fishing for drug targets from a
significant portion of the human genome, Lei Xie cautioned that “it is
especially challenging to validate weak drug-target interactions both
computationally and experimentally.” He added that modeling such drug
actions requires that scientists find relevant proteins and then examine them in
the context of a biological network, while at the same time simulating their
cumulative effects.
“This is indeed
challenging, but uncovering which protein receptors Nelfinavir binds to may help
us design better anti-cancer drugs,” said Bourne. “It is hard not to
believe that this broad-based systems approach represents the future of drug
discovery, at least as far as small-molecule drugs are concerned.”
(AP) – 30 April, 2011
SALT LAKE CITY (AP) —
Researchers at
The twin identical baby
boys received a tainted transfusion and both became HIV-positive a few years
ago.
Now, one of the twins has
a near-normal immune system and pretty good health, while the other boy is five
years behind him on the growth chart and has experienced a number of
complications.
That provocative
difference became the foundation of one of the studies, as researchers led by
BYU biology department chairman Keith Crandall try to figure out how the virus
changed in each twin. They've been joined in the study by scientists at the
National Cancer Institute.
Crandall said there are
competing theories about the differences in their clinical outcomes. One theory
is that natural selection drives it, so the results should be similar. The other
holds that random genetics plays a role and it therefore cannot be predicted.
A second study focuses on
an HIV vaccine scientists in
"I think the HIV
community is still split in terms of how to pursue treatment against HIV
infection," Crandall told the Deseret News.
"There is a strong
camp that thinks vaccine is still the way to go. We need to do more intelligent
vaccine design," carefully considering everything they've learned in other
attempts to create a vaccine that works.
"Others say no
way," he said. "The focus needs to be on drug therapy. But the virus
tends to hide out in places where drugs can't get to them."
The final study is led by
Greg Burton, chairman of BYU's Department of Chemistry and Biochemistry, and
Xueyuan Zho, a student at the
"The importance of
this study is that we moved ahead from earlier research. The effect was known,
but we showed the mechanism,"
Information from:
Copyright © 2011 The
Associated Press. All rights reserved.
April 26, 2011
Thanks to a program
pioneered in
HAART, which stands for
highly active antiretroviral therapy, uses triple-drug therapy to stop HIV in
its tracks. B.C. has been using HAART treatment as prevention since 1996, with
dramatic results. “While an outright cure for HIV remains elusive, HAART has
transformed HIV infection from a short-term death sentence into a chronic,
manageable condition and helped restore the health of thousands in
The B.C. Centre for
Excellence in HIV/AIDS pioneered the concept of Treatment as Prevention and
proved that it not only transforms HIV infection into a long-term chronic
manageable disease, it also dramatically decreases HIV transmission rates. HAART
therapy is available across
Here’s the impact the
program has had in BC: In the early 1990s, at least one British Columbian per
day was dying of AIDS. Since HAART’s introduction in 1996, AIDS-related
mortality has fallen by more than 90 per cent among those receiving treatment,
says Dr. Montaner, who is also chair in AIDS research and head of division of
AIDS at the
“In appropriately
treated individuals, HAART reduces the concentration of HIV present in plasma
and in sexual fluids to levels so low as to be undetectable by the best
commercially available tests,” says Montaner.
Reducing the infection allows people’s immune systems to recover and stops the
progression of HIV disease and even AIDS.
(AFP) – Apr 19, 2011
The CDC described the
results as "disappointing," and in a Monday statement said the trial's
monitoring committee had decided it "could not demonstrate efficacy even if
it continued to its originally planned conclusion."
A similar oral treatment,
known as pre-exposure prophylaxis (PrEP) for HIV prevention, has shown promise
in men who have sex with men.
The trial included 2,000
African women in
Researchers said that the
rate of new HIV infections in both the drug and placebo groups was the same,
with 56 new HIV cases equally distributed across both sections of the study.
They also noted that the
overall pregnancy rate among women in the study was nine percent, with the
highest rates seen in women taking birth control pills. More study is needed to
determine if the anti-HIV treatment had a disabling effect on the oral
contraceptives.
"Given today's
results, CDC cautions against women using PrEP for HIV prevention at this
time," the
"We will not know if
PrEP is effective for women, couples, or injection drug users until the
conclusive results of this and other trials are reported."
Copyright © 2011 AFP.
Activists from a
non-governmental organisation (NGO) light candles during an AIDS awareness
campaign ahead of World AIDS Day in Agartala, capital of
Credit: Reuters/Jayanta
Dey
Apr 25, 2011
And as the HIV virus
replicates, the risk increases, added the study, published in Archives of
Internal Medicine.
"Health care
providers traditionally think of HIV and its therapies increasing the risk of
atherosclerotic heart disease," said lead author Adreel Butt, at the
University of Pittsburgh School of Medicine in
"The surprising
finding from our study was the association of HIV with heart failure in the
absence of prior coronary heart disease."
The study involved nearly
8,500 adults, with a median age of 48 years in both HIV infected subjects and
controls.
The HIV group was more
likely to also be infected with Hepatitis C, 31 percent to 11 percent, and to
abuse cocaine -- 22 percent to 16 percent.
They were also more likely
to be smokers but less likely to have hypertension or diabetes.
During a median follow-up
of 7.3 years, 286 people developed heart failure. Rates of heart failure per
1,000 person-years, adjusted for age as well as race and ethnicity, were 7.12
for HIV patients and 4.82 for the controls.
After accounting for
traditional risk factors, the hazard ratio for heart failure with HIV was 1.81.
In addition, ongoing
replication of the virus led to a significantly higher risk of heart failure.
"On the other hand,
if HIV replication is well controlled, then the risk of heart failure is closer
to that seen among HIV-uninfected persons," Butt said.
The exact mechanism by
which HIV infection is linked to heart failure remains unclear, but possible
explanations include the direct effects of the HIV infection, antiretroviral
treatment that leads to an increased risk of coronary heart disease, and
nutritional deficiencies.
"Our results suggest
that HIV itself is playing an important and independent role," Butt and her
colleagues wrote.
The message for HIV care
providers is clear, though.
"Be on the lookout
for early signs of heart failure in HIV-infected persons, even if there is no
history of preceding coronary heart disease," Butt told Reuters Health.
"Controlling HIV well
may reduce the risk of heart failure."
(Reporting by Megan Brooks
at Reuters Health; editing by Elaine Lies)
(AP) – 26 April, 2011
WASHINGTON (AP) —
Federal health officials said Tuesday a highly anticipated hepatitis C drug from
Vertex Pharmaceuticals successfully treats the majority of patients with the
virus in less time than older medicines that have been used for 20 years.
The Food and Drug
Administration posted its review of Vertex's telaprevir ahead of a meeting
Thursday where outside experts will vote on the benefits of the experimental
drug. On Wednesday the experts will review a similar drug from Merck & Co.
Inc.
Both new drugs work by
blocking the enzyme protease, which allows the hepatitis virus to reproduce. The
new approach represents a breakthrough from older medicines, which are designed
to help boost the immune system to fight hepatitis.
Like HIV drugs, the new
drugs will be prescribed as part of a cocktail with the two older drugs to help
lower viral levels.
"A drug like
telaprevir does an amazing job clearing the virus, but there's a small portion
that is just intrinsically less responsive and it's the job of the older drugs
to clear up that mess that's left behind," said Dr. Camilla Graham,
Vertex's vice president for global medical affairs.
The current two-drug
treatment for the virus cures only about 40 percent of people and causes side
effects like nausea, fatigue and vomiting.
FDA scientists said 79
percent of first-time hepatitis C patients taking telaprevir and the older
medicines were cured, compared to 46 percent of those taking the older
medications alone, according to Vertex's studies. Among patients who had already
been treated for hepatitis C once, 65 percent achieved a cure after taking
telaprevir, compared with 17 percent of those taking the older medications.
In general, telaprevir's
cure rates are higher than those seen with Merck's boceprevir. The two drugs are
expected to compete in a multibillion dollar global market.
Shares of Vertex
Pharmaceuticals Inc. rose $5.96, or 12.4 percent, to $54 in midday trading.
Vertex's studies were
designed to show that adding telaprevir to the older drug combination could cure
most patients in six months — cutting the standard treatment time in half and
reducing exposure to negative side effects.
According to the FDA, 58
percent of new patients were eligible for this shorter treatment regimen based
on reduced viral levels after four or 12 weeks. The FDA's review states that
patients who have previously been treated for the disease should respond
similarly.
FDA notes that the drug
was significantly less effective for African Americans. The most common side
effect with the drug was a skin rash and fatigue.
The agency will ask its
panel to comment on those issues on Thursday. The FDA is not required to follow
the advice of its panelists, though it usually does
Hepatitis C is a major
cause of liver transplants, and it kills about 12,000
The disease is often
associated with users of illegal injectable drugs like heroin, though it could
also be picked up from blood transfusions before 1992, when testing of the blood
supply began.
Most people with hepatitis
C don't even know they have the virus until years later when liver damage has
occurred, which can cause abdominal pain, fatigue, itching and dark urine.
Vertex Pharmaceuticals is
based in
Copyright © 2011 The
Associated Press. All rights reserved.
(AP) – 28 April, 2011
William Weldon, who became
CEO in 2002, said the series of "disappointing recalls" troubled him
and employees and meant thousands of parents could not get medicines they needed
for their children.
Since September 2009, the
company has had about two dozen recalls of prescription and nonprescription
medicines, replacement hips, contact lenses and diabetes test strips, including
tens of millions of bottles of children's and adult Tylenol and Motrin.
Many of those
nonprescription drugs were made at a nonprescription medicine factory in
"You would be right
to ask if we made mistakes, and yes, we did," Weldon said. "Our goal
is to restore McNeil Consumer Health Care to the highest level of quality ...
thus restoring confidence in McNeil."
Weldon, 62, said J&J
has inspected 120 plants around the world and invested millions to improve the
quality of its manufacturing and satisfy federal regulators, who have three of
its factories under scrutiny. J&J has shifted manufacturing of some products
to other factories.
Roughly 1,300 shareholders
packed into four different rooms at a hotel opposite J&J's headquarters
seemed satisfied with Weldon's explanation of the recalls and what J&J has
been doing to rectify the problems. The audience clapped repeatedly during his
comments and lengthy presentations about the company's financial results and
innovative medicines and medical devices in development.
Analyst Steve Brozak of
WBB Securities said Weldon handled the mostly elderly shareholders at the
meeting well. Weldon opened with news of a deal reached Wednesday for a huge
acquisition, a big hike in J&J's generous quarterly dividend and the recent
settlement of a long arbitration battle with Merck & Co.
Shareholders also were
treated to goody bags full of Johnson & Johnson products and a fancy food
spread.
"It's bread and
circuses," Brozak said. "If it was any other company that had gone
through this, they would not have been able to leave an annual shareholders
meeting unscathed."
But after 2 1/4 hours of
speeches, slideshows and testimonials about J&J products and health care
programs, only six people in the audience asked questions or made comments.
"When I look at
what's been happening at J&J over the last couple of years, I see a
fundamental attack on the credo," Tom Williamson told Weldon.
He referred to J&J's
corporate pledge, displayed prominently at headquarters, that stresses
responsibility to patients, doctors and nurses.
"Your company tried
to do a stealth recall of Motrin," he added.
Congress has been
investigating that 2008 incident, in which J&J paid a third company to
quietly buy up faulty Motrin packets, rather than issuing a recall.
But another shareholder,
Kathleen Bennett, told Weldon she appreciates his efforts to fix the
recall-related problems.
"I say, Mr. Bill
Weldon, well done," she said, drawing loud applause.
About 90 percent of
shareholders voted for a J&J proposal to give them an advisory vote every
year on compensation for top officers.
Yet only 61 percent
supported the company proposal for advisory approval of its executive
compensation policies and the compensation top officers received last year.
Weldon's 2010 pay package was worth more than $23 million, down about $2.5
million after two unprecedented years of revenue declines.
Stockholders voted down
all three shareholder proposals on the agenda, each by 95 percent or more.
One, by the Sisters of
Charity of Saint Elizabeth and other religious groups, would have restricted
future prescription drug price increases sharply. Another would have expanded
J&J's employment nondiscrimination policy to include people with health
problems, but J&J said its broad policy is sufficient.
The third would have
required ending use of animals in training surgeons to use J&J's high-tech
surgical tools; Weldon said J&J already tries to use alternatives when
possible. That proposal was presented by Alka Chandna, a spokeswoman for People
for the Ethical Treatment of Animals. The group had four picketers outside the
hotel protesting on the issue, two in big pink piggy suits because pigs are
sometimes used in surgical training.
A second group of three
medical students picketed beside them, because J&J has not agreed to join an
international "medicine patent pool" that would make it easier and
cheaper for generic drugmakers to produce inexpensive HIV medicines for
developing countries.
Weldon told the audience
an acquisition reached the day before is J&J's biggest ever. J&J agreed
to buy U.S.-Swiss medical device maker Synthes Inc. for $21.3 billion. The deal
would give J&J a much bigger share of the market for surgical trauma
equipment and orthopedic implants.
"It is consistent
with our long-term strategy to strengthen our leadership position around the
world," Weldon said.
"Our pipeline today
is considered one of the best in the industry," Weldon added.
Meanwhile, J&J's board
decided to raise the quarterly dividend on company stock by 5.6 percent, from 54
cents to 57 cents per share.
In trading Thursday,
shares of the company fell 19 cents to $65.38.
Copyright © 2011 The Associated Press. All rights reserved.