Once again, this does not address the primary problem, inflammation. Since your brain contains 20% of the body's cholesterol I'd be concerned about your brain functioning correctly. How will this research monitor monkey cognition? Ok, I seem to be wrong on this: Simply put: low blood cholesterol does not cause low brain cholesterol.
A ‘Cure for Heart Disease’? A Single Shot Succeeds in Monkeys
A novel gene-editing experiment seems to have permanently reduced LDL and triglyceride levels in monkeys.
What if a single injection could lower blood levels of cholesterol and triglycerides — for a lifetime?
In
the first gene-editing experiment of its kind, scientists have disabled
two genes in monkeys that raise the risk for heart disease. Humans
carry the genes as well, and the experiment has raised hopes that a
leading killer may one day be tamed.
“This
could be the cure for heart disease,” said Dr. Michael Davidson,
director of the Lipid Clinic at the University of Chicago Pritzker
School of Medicine, who was not involved in the research.
But
it will be years before human trials can begin, and gene-editing
technology so far has a mixed tracked record. It is much too early to
know whether the strategy will be safe and effective in humans; even the
monkeys must be monitored for side effects or other treatment failures
for some time to come.
The
results were presented on Saturday at the annual meeting of the
International Society for Stem Cell Research, this year held virtually
with about 3,700 attendees around the world. The scientists are writing
up their findings, which have not yet been peer-reviewed or published.
The
researchers set out to block two genes: PCSK9, which helps regulate
levels of LDL cholesterol; and ANGPTL3, part of the system regulating
triglyceride, a type of blood fat. Both genes are active in the liver,
which is where cholesterol and triglycerides are produced. People who inherit mutations that destroyed the genes’ function do not get heart disease.
People
with increased blood levels of triglycerides and LDL cholesterol have
dramatically greater risks of heart disease, heart attacks and strokes,
the leading causes of death in most of the developed world. Drug
companies already have developed and are marketing two so-called PCSK9
inhibitors that markedly lower LDL cholesterol, but they are expensive
and must be injected every few weeks.
Researchers
at Verve Therapeutics, led by Dr. Sekar Kathiresan, the chief
executive, decided to edit the genes instead. The medicine they
developed consists of two pieces of RNA — a gene editor and a tiny guide
that directs the editor to a single sequence of 23 letters of human DNA
among the genome’s 3.25 billion so-called base pairs.
The
RNA is shrouded in tiny lipid spheres to protect the medicine from
being instantly degraded in the blood. The lipid spheres travel directly
to the liver where they are ingested by liver cells. The contents of
the spheres are released, and once the editor lands on its target, it
changes a single letter of the sequence to another — like a pencil
erasing one letter and writing in another.
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Not
only did the system work in 13 monkeys, the researchers reported, but
it appeared that every liver cell was edited. After gene editing, the
monkeys’ LDL levels dropped by 59 percent within two weeks. The ANGPTL3
gene editing led to a 64 percent decline in triglyceride levels.
One
danger of gene editing is the process may result in modification of DNA
that scientists are not expecting. “You will never be able to have no
off-target effects,” warned Dr. Deepak Srivastava, president of the
Gladstone Institutes in San Francisco.
In
treating a condition as common as heart disease, he added, even an
uncommon side effect can mean many patients are affected. So far,
however, the researchers say that they have not seen any inadvertent
editing of other genes.
Another
question is how long the effect on cholesterol and triglyceride levels
will last, Dr. Davidson said. “We hope it will be one-and-done, but we
have to validate that with clinical trials,” he said.
Jennifer
Doudna, a biochemist of the University of California, Berkeley, and a
discoverer of Crispr, the revolutionary gene editing system, said: “In
principle, Verve’s approach could be better because it’s a one-time
treatment.”
But it is much too soon to say if it will be safe and long-lasting, she added.
If
the strategy does work in humans, its greatest impact may be in poorer
countries that cannot afford expensive injections for people at high
risk of heart disease, said Dr. Daniel Rader, chairman of the department
of genetics at the University of Pennsylvania and a member of Verve’s
scientific advisory board.
Dr.
Kathiresan, of Verve, noted that half of all first heart attacks end in
sudden death, making it imperative to protect those at high risk.
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Dr.
Kathiresan began the research at the Massachusetts General Hospital and
the Broad Institute, where he and his colleagues found a collection of
genes that increase risk of heart attack at a relatively young age, as
well as eight genes that, when mutated, decrease risk.
Those
protective genes, he reasoned, could be targets for gene editing if
there were a way to alter them in people. Gene editing is only now
succeeding, and so far its successes have been in rare diseases.
Other
investigators and companies have tried editing genes in mice to prevent
heart disease, with some success, but primates are a much more
difficult challenge.
Dr. Kathiresan
said that to his knowledge, his study is the first to use the
pencil-and-eraser type gene editing in primates for a very common
disease. Verve licensed the technology, called base editing, from Beam
Therapeutics.
If all goes well, Dr.
Kathiresan hopes in a few years to begin treating people who have had
heart attacks and still have perilously high cholesterol. For them, the
risk of another heart attack is so high that the possible benefit may
far outweigh the risks of the treatment.
Heart
disease generally occurs only after decades of high cholesterol levels,
Dr. Davidson noted. By age 50, people most likely to have a heart
attack already have a significant accumulation of plaque in their
arteries.
But if the PCSK9 gene could be knocked out in 20-year-olds, he said, “there would be no heart disease in their future.”
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