News (Updated
September 25, 2011)
[Home]
[Previous
news]
Sep 19 2011
By Deena Beasley
(Reuters) - An early stage
trial of Sangamo BioSciences Inc's HIV treatment found that the gene therapy
reduced levels of the virus and even eliminated it in one patient with a
naturally occurring gene mutation.
The very small Phase 1
trial tested the SB-728-T gene therapy, which is designed to disrupt the CCR5
gene used by HIV to infect cells of the immune system.
If shown to be safe and
effective, the treatment could end the need for the antiretroviral drugs now
used to keep the virus that causes AIDS in check by suppressing viral
replication in the blood.
Trial results presented in
In a statement, June said
the results suggest the need to increase the frequency of the modified cells in
HIV-infected patients, which could lead to a "functional cure" for
AIDS, but the means of achieving this have not been clarified.
Sangamo said earlier this
year that a single infusion of the treatment improved immune system damage in
nearly all of the subjects analyzed in the first trial of the therapy in humans.
The 10 patients in the
trial were on antiretroviral therapy when the study began. After four weeks, six
of them went on a "treatment interruption," during which they stopped
taking antiviral medication for 12 weeks.
Viral load decreased in
three of the six subjects, with one patient's viral load reduced to undetectable
levels. That patient carried a naturally occurring mutation in one copy of his
CCR5 gene.
Humans contain two copies
of each gene, one from the father and one from the mother, which sometimes are
referred to as the alleles of a gene.
"Since one copy of
his gene was already disrupted naturally, twice as many of his cells were 'biallelically'
modified," Sangamo Chief Executive Officer Edward Lanphier said in a
telephone interview, meaning that both members of the CCR5 gene pair were
knocked out.
He estimated that between
5 percent and 10 percent of HIV patients carry the genetic mutation.
Around 33 million people
worldwide have the human immunodeficiency virus (HIV) that causes AIDS.
Lanphier said Sangamo will
move ahead with a strategy to maximize the number of cells that can be "biallelically"
modified by SB-728-T. Options include targeting only the small segment of
patients with mutated CCR5 genes or using "strategies that boost the amount
of engraftment of modified cells."
Sep 19 2011
(Reuters) - Gilead
Sciences Inc's four-drug experimental HIV pill worked as well as a regimen
containing protease inhibitor Reyataz in the second pivotal trial of the drug,
the company said on Monday.
Although the trial
succeeded, it did not show the experimental pill, called the Quad, was superior
to the Reyataz regimen and
"Overall the data are
good ... mostly in line with investor expectations," said Cowen and Co
analyst Philip Nadeau.
"I think there might
of been a little bit of expectation for statistical superiority, but only from a
few outliers."
The trial found that 90
percent of patients taking the
The four-drug pill --
which combines experimental integrase inhibitor elvitegravir and boosting agent
cobicistat with Truvada, a pill consisting of Gilead's older HIV drugs Emtriva
and Viread -- is seen as the biotechnology company's most important pipeline
product.
The company said it plans
to file for
Gilead Chief Operating
Officer John Milligan, speaking on a conference call, said the company will
request a "priority review" by the Food and Drug Administration, which
could clear the way for an approval as early as mid-year 2012.
(Reporting by Deena
Beasley in
Sep 20 2011
By Kate Kelland
Researchers from the
"It's like an army
that has lost its weapons but still has flags, so another army can recognize it
and attack it," said Adriano Boasso of Imperial College London, who led the
study.
The team now plans to
investigate how to use this way of inactivating the virus and possibly develop
it into a vaccine.
Usually when a person
becomes infected with HIV, the body's innate immune response puts up an
immediate defense. But some researchers believe HIV causes the innate immune
system to overreact. This weakens the immune system's next line of defense,
known as the adaptive immune response.
For this study --
published on Monday in the journal Blood -- Boasso's team removed cholesterol
from the membrane around the virus and found that this stopped HIV from
triggering the innate immune response. This in turn led to a stronger adaptive
response, orchestrated by a type of immune cells called T cells.
AIDS kills around 1.8
million people a year worldwide. An estimated 2.6 million people caught HIV in
2009, and 33.3 million people are living with the virus.
Major producers of current
HIV drugs include Gilead Bristol Myers Squibb, Merck, Pfizer and GlaxoSmithKline.
Scientists from companies,
non-profits and governments around the world have been trying for many years to
make a vaccine against HIV but have so far had only limited success.
A 2009 study in
An American team working
on an experimental HIV vaccine said in May that it helped monkeys with a form of
the AIDS virus control the infection for more than a year, suggesting it may
lead to a vaccine for people.
HIV is spread in many ways
-- during sex, on needles shared by drug users, in breast milk and in blood --
so there is no single easy way to prevent infection. The virus also mutates
quickly and can hide from the immune system, and attacks the very cells sent to
battle it.
"HIV is very
sneaky," Boasso said in a statement. "It evades the host's defenses by
triggering overblown responses that damage the immune system. It's like revving
your car in first gear for too long -- eventually the engine blows out.
He said this may be why
developing a vaccine has proven so tricky. "Most vaccines prime the
adaptive response to recognize the invader, but it's hard for this to work if
the virus triggers other mechanisms that weaken the adaptive response."
HIV takes its membrane
from the cell that it infects, the researchers explained in their study. This
membrane contains cholesterol, which helps keep it fluid and enables it to
interact with particular types of cell.
Normally, a subset of
immune cells called plasmacytoid dendritic cells (pDCs) recognize HIV quickly
and react by producing signaling molecules called interferons. These signals
activate various processes which are initially helpful, but which damage the
immune system if switched on for too long.
Working with scientists
ONLINE gamers have
achieved a feat beyond the realm of Second Life or Dungeons and Dragons: they
have deciphered the structure of an enzyme of an AIDS-like virus that had
thwarted scientists for a decade.
The exploit was published
yesterday in the journal, Nature Structural & Molecular Biology, where -
exceptionally in scientific publishing - both gamers and researchers are
honoured as co-authors.
Their target was a
monomeric protease enzyme, a cutting agent in the complex molecular tailoring of
retroviruses, a family that includes HIV.
Figuring out the structure
of proteins is vital for understanding the causes of many diseases and
developing drugs to block them.
But a microscope gives
only a flat image of what to the outsider looks like a plate of one-dimensional
scrunched-up spaghetti. Pharmacologists, though, need a 3-D picture that
"unfolds" the molecule and rotates it in order to reveal potential
targets for drugs.
This is where Foldit comes
in.
Developed in 2008 by the
To the astonishment of the
scientists, the gamers produced an accurate model of the enzyme in just three
weeks.
Cracking the enzyme
"provides new insights for the design of antiretroviral drugs", says
the study, referring to the lifeline medication against the human
immunodeficiency virus (HIV).
It is believed to be the
first time that gamers have resolved a long-standing scientific problem.
"We wanted to see if
human intuition could succeed where automated methods had failed," Firas
Khatib of the university's biochemistry lab said in a press release.
"The ingenuity of
game players is a formidable force that, if properly directed, can be used to
solve a wide range of scientific problems."
One of Foldit's creators,
Seth Cooper, explained why gamers had succeeded where computers had failed.
"People have spatial
reasoning skills, something computers are not yet good at," he said.
"Games provide a
framework for bringing together the strengths of computers and humans. The
results in this week's paper show that gaming, science and computation can be
combined to make advances that were not possible before."
22 September 2011
(BBC news) Scientists have
gained new knowledge into how viruses such as flu and HIV jump between species.
The research, by
The scientists wanted to
understand how viruses such as bird flu infect distant species like humans.
They found they were
better able to infect species closely related to their typical target species
than species that were distantly related.
However, the research also
suggested that when diseases make a big leap they may then spread easily in
species closely related to the new victim, regardless of how closely related
these are to the original target species.
Dr Ben Longdon, of
"Understanding how
diseases jump between different species is essential if we want to predict the
appearance of new diseases in the future."
More susceptible
By infecting more than 50
species of flies with three different viruses, the researchers showed that
species closely related to a virus's usual target species were more susceptible
than distantly related flies.
They also showed that
groups of flies that were closely related were similarly susceptible to the same
viruses.
The study, funded by the
Biotechnology and Biological Sciences Research Council, Natural Environment
Research Council, the Wellcome Trust and the Royal Society, was published in the
journal PLoS Pathogens.
By Michael Smith, North American Correspondent, MedPage Today
Published: September 23, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of
Medicine,
Action Points
Note that
this study was published as an abstract and presented at a conference. These
data and conclusions should be considered to be preliminary until published
in a peer-reviewed journal.
Explain that
an antibody approach to HIV treatment was safe and well tolerated, but
reduced viral loads in less than half of treatment-experienced patients.
Note that the
humanized monoclonal antibody studied, ibalizumab, binds to CD4-positive T
cells and blocks the entry of HIV, and is the first monoclonal antibody to
be tested as an HIV therapy.
The compound,
dubbed ibalizumab, is a humanized monoclonal antibody that binds to CD4-positive
T cells and blocks the entry of HIV, according to Stanley Lewis, MD, of TaiMed
Biologics
It's the
first monoclonal antibody to be tested as an HIV therapy, Lewis reported at the
Interscience Conference on Anti-Microbial Agents and Chemotherapy.
Other
so-called entry inhibitors have been developed and one – maraviroc (Selzentry)
– is approved, but they have been aimed at the CCR5 co-receptor on CD4 cells
and are not antibodies.
Ibalizumab,
on the other hand, binds to part of the CD4 receptor itself, rather than CCR5 or
CXCR4, the other co-receptor used by HIV to enter cells. Lewis said the exact
mechanism of action is not yet clear, although ibalizumab does not stop HIV from
attaching to target cells.
A previous
study showed ibalizumab was better than placebo at suppressing the virus and
this study was aimed at comparing safety, tolerability, and efficacy of two
different doses of the compound -- 800 milligrams every two weeks or 2,000
milligrams every four weeks, delivered intravenously.
The primary
endpoint was the proportion of patients with a plasma viral load of less than 50
copies of HIV RNA per milliliter after 24 weeks of treatment, Lewis said.
The
researchers enrolled 113 patients, all of them with resistance to at least one
drug in each of the three main HIV medication classes, and all with a plasma
viral load of more than 1,000 copies of HIV RNA per milliliter.
"They
were all failing their regimens," Lewis said.
After 24
weeks of treatment, Lewis reported:
The
proportion of those meeting the primary endpoint was 44% for the 800-milligram
dose and 28% for those getting the higher dose, although the difference was not
statistically significant.
The median
drop in viral load was 1.6 log for the low dose and 1.8 log for the high dose,
again without statistical significance.
There were 15
serious adverse events, but investigators found they weren't related to the
drug. No patient stopped therapy because of adverse events related to therapy
and there were no clinically meaningful laboratory abnormalities.
The most
common treatment-emergent side effects were rash, diarrhea, headache, and nausea
– mostly mild or moderate -- with no significant difference between the doses.
Still, the
drug may have difficulty finding a place in treatment, even if later clinical
trials confirm these results, Jean-Michel Molina, MD, of
"I was
surprised by the overall low response rate," Molina told MedPage Today.
"Less than 50% achieving a viral load of below 50 is not a good
response."
The compound,
while apparently relatively well tolerated, still has some side effects, he
said, and it must be delivered either intravenously or subcutaneously. At the
same time, many newer drugs deliver much better responses, he added.
"So you wonder what's the real benefit of this drug (and) which patients might be able to use it," Molina said.
HIV vaccines are in their
infancy, and effective microbicides to prevent sexual transmission of HIV still
don't exist. Protection is especially needed for women, who make up nearly half
of all global cases. Researchers at Children's Hospital Boston envision a new
way for women to protect themselves before sex: an applicator filled with
specially formulated fatty particles called liposomes.
In tests led by Daniel
Kohane, M.D., Ph.D., director of the Laboratory for Biomaterials and Drug
Delivery at Children's Hospital Boston, liposomes inhibited HIV infection in
cell culture and appeared safe in female mice when injected intravaginally. The
findings are reported in the November issue of the journal Biomaterials,
published online September 19.
Liposomes are spherical
particles with a double outer layer of lipids (fats) and hollow centers. They
are relatively easy and cheap to engineer, and thus present a viable option for
developing countries, where the cost of anti-HIV drugs bars access for most
people.
Liposomes can be filled
with drugs or other compounds, but in this case, Kohane and colleagues found, to
their surprise, that the liposomes alone were effective in blocking infection.
"We had been planning
do much more complex things, like putting ligands on the surface to increase
binding to HIV," says Kohane. "It was a surprise that liposomes alone
worked so well. Simplicity is always better - if liposomes work by themselves,
we may not need anything else, and it would be cheaper and potentially much
safer."
Kohane and colleagues hope
to conduct further tests to better understand how the liposomes are blocking
infection. They bind to HIV, perhaps interfering with the virus's ability to
fuse with cell membranes, the first step in infection.
"The idea,
simplistically, is that liposomes look like cell membranes," says Kohane,
"so maybe we could use them as decoys to prevent HIV infection."
Kohane and colleagues
formulated a range of liposomes using various naturally occurring and synthetic
lipids and screened them systematically in cell cultures. Several formulations
showed a good therapeutic profile, protecting the cells from HIV infection
without being toxic. Especially effective were liposomes containing cardiolipin,
a fat that was first found in animal hearts; performance was further improved by
adding a synthetic phospholipid.
Tested in female mice,
these formulations caused little or no inflammation, which can compromise the
vaginal lining and increase the risk of HIV transmission. Imaging confirmed that
the liposomes remained in place or left the body, but did not travel beyond the
vagina.
"This research makes
an important contribution towards creating a safe and effective form of HIV
prevention for women," says Nikita Malavia, Ph.D., the study's first
author, who worked in Kohane's lab and in the lab of Robert Langer, ScD, of MIT.
"Women in areas such as sub-Saharan Africa often cannot control their male
partners' use of condoms, making them three times more likely to be HIV-positive
than men. This technology could enable women to take control in their own
hands."
Though some intravaginal
compounds are in the pipeline, none are available yet. The advantage of using
liposomes is that they are inexpensive, easy to formulate into ointments or
gels, and stable for long periods of time, making them a particularly good
option in resource-poor settings.
Kohane hopes to get
further funding to test liposome formulations in other animal models.
The study was funded by
the Grand Challenges in Global Health initiative and the National Institutes of
Health.
About Children's Hospital
BostonChildren's Hospital Boston is home to the world's largest research
enterprise based at a pediatric medical center, where its discoveries have
benefited both children and adults since 1869. More than 1,100 scientists,
including nine members of the National Academy of Sciences, 11 members of the