How long before this is proven and rolled out to patients?
http://www.alphagalileo.org/ViewItem.aspx?ItemId=163251&CultureCode=en
An American mother’s hunch might result in new treatments
for patients who can’t tolerate conventional cholesterol-lowering drugs.
An American mother with twin daughters with a rare incurable disease
may seem like an unlikely partner in cholesterol research. But when
Chris Hempel read about the role of cholesterol crystals in heart
disease in 2010, she immediately thought of her daughters Addison and
Cassidy, whose cells are unable to get rid of cholesterol.
Perhaps the experimental drug that was being used to treat her girls
could also treat people with heart disease? She contacted Eicke Latz,
the University of Bonn researcher behind the study, and suggested he
look into the idea. Latz is also an assistant professor at NTNU’s Centre
of Molecular Inflammation Research (CEMIR).
Six years later,
Hempel’s hunch has been confirmed: in a paper published in early April
in Science Translational Medicine, Latz and an international team
reported that the drug cyclodextrin can dissolve cholesterol crystals so
they can be excreted by the body. The drug also changes the way the
body’s immune system responds to the presence of cholesterol crystals,
reducing inflammation in artery walls. Hempel is listed as one of the
co-authors.
Although there already are different medicines on the market that can
treat high cholesterol, some people experience side effects from these
drugs. Cyclodextrin thus offers a potential new therapy for
cardiovascular disease, Latz and his colleagues say.
Disappearing plaque
Your body needs (and makes) cholesterol in
small amounts, but too much cholesterol can lead to hardening of the
arteries, or atherosclerosis. Atherosclerosis is when artery walls are
coated in plaque, which is made of a mix of cholesterol, calcium and
other substances. The plaque makes arteries less flexible and causes
them to narrow, thereby reducing blood flow. Eventually the arteries may
be completely closed off by a blood clot, which can cause a stroke or
heart attack.
In the 2010 study that caught Hempel’s attention, researchers
reported how cholesterol crystals were found to cause inflammation in
arteries, which then led to atherosclerosis. When Latz and his
collaborators, including Terje Espevik, head of CEMIR, heard Hempel’s
idea to test cyclodextrin, they “jumped on it,” Espevik said.
Tested in mice and in human plaques
The researchers tested
cyclodextrin in mice that were fed a cholesterol-rich diet and that were
prone to develop atherosclerosis.
“We saw that cyclodextrin prevented plaque formation. It even reduced
the existing plaque the mice had in their arteries,” Espevik said.
To see if the drug would also work in human tissue, CEMIR postdoc
Siril Bakke was given access to a biobank, collected by Bente Halvorsen
from the University of Oslo, OUS Rikshospitalet, with plaque biopsies
taken from human carotid arteries. When Bakke examined biopsies of
plaques treated with cyclodextrin, she found that the cholesterol was
removed from the plaques. The cells in the plaque were also reprogrammed
so they were in a reduced inflammatory state.
Soaked up cholesterol and removed it
Another
positive effect of cyclodextrin was that it reprogrammed macrophages,
immune cells in the body that remove foreign or bad substances, Espevik
said.
“What cyclodextrin did was to reprogram the macrophage so it didn’t
create such a big inflammatory response,” Espevik said. That meant the
macrophage could soak up excess cholesterol and remove it, while
reducing the inflammation in the artery walls and thus reducing the
likelihood of causing a plaque to form.
That means that cyclodextrin works via two mechanisms, Espevik said.
The first is to dissolve cholesterol crystals so the body can excrete
them, and the second is to reduce the inflammatory response in artery
walls when macrophages soak up cholesterol crystals.
Promising therapeutic approach
The findings were so positive that
the research team is now hoping to find funding and an industrial
partner to conduct clinical trials in humans, Espevik said.
Latz estimates it will take approximately EUR 1 million to do the
trials. One potential drawback is also one of the most positive aspects
of cyclodextrin: the substance, which is a type of sugar, has already
been approved by the US Food and Drug Administration for use in humans.
But because it has been in existence for some time, it cannot be
patented. That makes it harder to get a drug company interested in
developing cyclodextrin to treat heart disease, but it also will make it
easier to get the drug approved to treat heart disease if the clinic
trials support the research findings.
In addition to Latz and Espevik and their colleagues at the
University of Bonn and NTNU, scientists from the University of Oslo/OUS
Rikshospitalet and from Australia, the USA, Denmark and Sweden
contributed to the research.
http://gemini.no/en/2016/04/dissolving-cholesterol-crystals-may-help-treat-heart-disease/
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