Scientists Identify Gene Responsible for Statin-Induced Muscle Pain 
Author Message
 Scientists Identify Gene Responsible for Statin-Induced Muscle Pain

Scientists Identify Gene Responsible for Statin-Induced Muscle Pain

Date: 11/27/2007
Contact: Bonnie Prescott
Phone: 617-667-7306

BOSTON - Statins, the popular class of {*filter*} used to lower
cholesterol, are among the most commonly prescribed medications in
developed countries. But for some patients, accompanying side effects
of muscle weakness and pain become chronic problems and, in rare
cases, can escalate to debilitating and even life-threatening damage.

Now a study led by investigators at Beth Israel Deaconess Medical
Center (BIDMC), helps explain the source of these problems. Published
in the December 2007 issue of The Journal of Clinical Investigation,
the findings offer the first evidence that a gene known as atrogin-1
plays a key role in statin-related muscle toxicity.

"Although it is not known exactly how many of the 500 million
individuals who take statins experience muscle pain and weakness,
muscle symptoms are generally considered the most common side effects
of these medications," explains co-senior author Vikas P. Sukhatme,
MD, PhD, Vice Chair of Medicine for Interdepartmental and
Translational Programs, Chief of the Division of Nephrology, and Chief
of the Division of Interdisciplinary Medicine and Biotechnology at
BIDMC.

"Statin users describe a wide spectrum of symptoms - at the most
extreme end is a severe breakdown of skeletal muscle known as
rhabdomyolysis," says Sukhatme, who is also the Victor J. Aresty
Professor of Medicine at Harvard Medical School (HMS). "At the other
end is 'grumbling muscles,' milder, more diffuse muscle soreness and
cramps. This kind of symptomatic muscle weakness and pain is quite
frequent, but often difficult to quantitate."

Known by such trade names as Lipitor, Zocor, Pavacol and Mevacor,
statins lower cholesterol by inhibiting HMG-CoA reductase, a key
enzyme in cholesterol synthesis.

Approximately five years ago, the study's co-senior author Stewart
Lecker, MD, PhD, and colleagues in the HMS laboratory of Alfred
Goldberg, MD, first discovered the atrogin-1 gene, so named for its
role in muscle atrophy.

"We learned that atrogin-1 is rapidly turned on in wasting muscle,"
explains Lecker, who is an investigator in the Division of Nephrology
at BIDMC and Assistant Professor of Medicine at HMS. Muscle wasting
occurs in a large number of disease states, including cancer, AIDS,
and kidney disease and can also occur when muscles are underused due
to injury or lack of exercise. "In the absence of atrogin-1
activation," he adds, "muscle atrophy is diminished."

Since this initial discovery, atrogin-1 has been found in every
existing model of muscle wasting, prompting Lecker and Sukhatme to
investigate whether cholesterol-lowering statins might also be
"turning on" this gene.

"We reasoned that since atrogin-1 plays a key role in the development
of wasting in skeletal muscle, it might also mediate part of
[patients'] sensitivity to statins," the authors write.

They proceeded to conduct three separate experiments to test this
hypothesis. They first examined the expression of the atrogin-1 gene
in biopsies of 19 human quadricep muscles from five control patients,
six patients with muscle pain who were not being treated with statins
and eight patients with muscle pain/damage who were using statins.
Their results showed that atrogin-1 expression was significantly
higher among the statin users.

Next, the scientists studied statins' effects on cultured muscle cells
treated with various concentrations of lovastatin. Compared with
control samples, the lovastatin-treated cells became progressively
thinner and more damaged. But remarkably, say the authors, the cells
lacking the atrogin-1 gene were resistant to statins' deleterious
effects.

Finally, the authors tested the drug in zebrafish. They showed that
just as in mammalian muscle cell culture, lovastatin led to muscle
damage, even at low concentrations; as the concentration was
increased, so too was the damage. And, once again, they observed that
fish lacking the atrogin-1 gene were resistant to statin-induced
damage.

"These three complementary experiments demonstrate that atrogin-1 has
a fundamental role in statin-induced toxicity," notes Lecker. "Future
experiments will be aimed at understanding how statins turn on the
atrogin-1 response in muscle, and in ascertaining what transpires in
muscle following atrogin-1 activation that leads to muscle damage and
atrophy. The hope is that eventually patients will be able to glean
statins' positive benefits to cholesterol metabolism and reduction of
cardiovascular events while being spared accompanying muscle
toxicities."

This study was funded, in part, by grants from the National Institutes
of Health.

Study coauthors include BIDMC investigators Jun-Ichi Hanai and Peirang
Cao (lead authors) and Preeti Tanksale; Shintaro Imamura, Eriko
Koshimizu and Shuji Kishi of Schepens Eye Research Institute; Michiaki
Yamashita, of the National Research Institute of Fisheries Science,
Yokohama, Japan; and Paul Phillips of Scripps Mercy Hospital, San
Diego, California.



Mon, 17 May 2010 10:48:21 GMT
 Scientists Identify Gene Responsible for Statin-Induced Muscle Pain

Quote:

> Scientists Identify Gene Responsible for Statin-Induced Muscle Pain

> Date: 11/27/2007
> Contact: Bonnie Prescott
> Phone: 617-667-7306

> BOSTON - Statins, the popular class of {*filter*} used to lower
> cholesterol, are among the most commonly prescribed medications in
> developed countries. But for some patients, accompanying side effects
> of muscle weakness and pain become chronic problems and, in rare
> cases, can escalate to debilitating and even life-threatening damage.

> Now a study led by investigators at Beth Israel Deaconess Medical
> Center (BIDMC), helps explain the source of these problems. Published
> in the December 2007 issue of The Journal of Clinical Investigation,
> the findings offer the first evidence that a gene known as atrogin-1
> plays a key role in statin-related muscle toxicity.

> "Although it is not known exactly how many of the 500 million
> individuals who take statins experience muscle pain and weakness,
> muscle symptoms are generally considered the most common side effects
> of these medications," explains co-senior author Vikas P. Sukhatme,
> MD, PhD, Vice Chair of Medicine for Interdepartmental and
> Translational Programs, Chief of the Division of Nephrology, and Chief
> of the Division of Interdisciplinary Medicine and Biotechnology at
> BIDMC.

> "Statin users describe a wide spectrum of symptoms - at the most
> extreme end is a severe breakdown of skeletal muscle known as
> rhabdomyolysis," says Sukhatme, who is also the Victor J. Aresty
> Professor of Medicine at Harvard Medical School (HMS). "At the other
> end is 'grumbling muscles,' milder, more diffuse muscle soreness and
> cramps. This kind of symptomatic muscle weakness and pain is quite
> frequent, but often difficult to quantitate."

> Known by such trade names as Lipitor, Zocor, Pavacol and Mevacor,
> statins lower cholesterol by inhibiting HMG-CoA reductase, a key
> enzyme in cholesterol synthesis.

> Approximately five years ago, the study's co-senior author Stewart
> Lecker, MD, PhD, and colleagues in the HMS laboratory of Alfred
> Goldberg, MD, first discovered the atrogin-1 gene, so named for its
> role in muscle atrophy.

> "We learned that atrogin-1 is rapidly turned on in wasting muscle,"
> explains Lecker, who is an investigator in the Division of Nephrology
> at BIDMC and Assistant Professor of Medicine at HMS. Muscle wasting
> occurs in a large number of disease states, including cancer, AIDS,
> and kidney disease and can also occur when muscles are underused due
> to injury or lack of exercise. "In the absence of atrogin-1
> activation," he adds, "muscle atrophy is diminished."

> Since this initial discovery, atrogin-1 has been found in every
> existing model of muscle wasting, prompting Lecker and Sukhatme to
> investigate whether cholesterol-lowering statins might also be
> "turning on" this gene.

> "We reasoned that since atrogin-1 plays a key role in the development
> of wasting in skeletal muscle, it might also mediate part of
> [patients'] sensitivity to statins," the authors write.

> They proceeded to conduct three separate experiments to test this
> hypothesis. They first examined the expression of the atrogin-1 gene
> in biopsies of 19 human quadricep muscles from five control patients,
> six patients with muscle pain who were not being treated with statins
> and eight patients with muscle pain/damage who were using statins.
> Their results showed that atrogin-1 expression was significantly
> higher among the statin users.

> Next, the scientists studied statins' effects on cultured muscle cells
> treated with various concentrations of lovastatin. Compared with
> control samples, the lovastatin-treated cells became progressively
> thinner and more damaged. But remarkably, say the authors, the cells
> lacking the atrogin-1 gene were resistant to statins' deleterious
> effects.

> Finally, the authors tested the drug in zebrafish. They showed that
> just as in mammalian muscle cell culture, lovastatin led to muscle
> damage, even at low concentrations; as the concentration was
> increased, so too was the damage. And, once again, they observed that
> fish lacking the atrogin-1 gene were resistant to statin-induced
> damage.

> "These three complementary experiments demonstrate that atrogin-1 has
> a fundamental role in statin-induced toxicity," notes Lecker. "Future
> experiments will be aimed at understanding how statins turn on the
> atrogin-1 response in muscle, and in ascertaining what transpires in
> muscle following atrogin-1 activation that leads to muscle damage and
> atrophy. The hope is that eventually patients will be able to glean
> statins' positive benefits to cholesterol metabolism and reduction of
> cardiovascular events while being spared accompanying muscle
> toxicities."

> This study was funded, in part, by grants from the National Institutes
> of Health.

> Study coauthors include BIDMC investigators Jun-Ichi Hanai and Peirang
> Cao (lead authors) and Preeti Tanksale; Shintaro Imamura, Eriko
> Koshimizu and Shuji Kishi of Schepens Eye Research Institute; Michiaki
> Yamashita, of the National Research Institute of Fisheries Science,
> Yokohama, Japan; and Paul Phillips of Scripps Mercy Hospital, San
> Diego, California.

"Next, the scientists studied statins' effects on cultured muscle
cells treated with various concentrations of lovastatin. Compared with
control samples, the lovastatin-treated cells became progressively
thinner and more damaged. But remarkably, say the authors, the cells
lacking the atrogin-1 gene were resistant to statins' deleterious
effects."

Because we all have the atrogin-1 gene, this observation in cultured
muscle cells would suggest that statins are inherently toxic to our
muscle cells.

For this reason, it remains wise to eat less, down to the optimal
amount in order to lose the VAT thereby obviating the need for
prolonged chronic exposure to statins which have the potential for
causing progressive muscle wasting in all of us.

Here is how to eat less, down to the optimal amount:

http://www.***.com/

Be hungry... be healthy... be hungrier... be blessed:

http://www.***.com/

Prayerfully in the infinite power and might of the Holy Spirit,

Andrew <><
--
Andrew B. Chung, MD/PhD
Lawful steward of http://www.***.com/
Bondservant to the KING of kings and LORD of lords.



Mon, 17 May 2010 13:25:16 GMT
 Scientists Identify Gene Responsible for Statin-Induced Muscle Pain
Andy Chungie,

Hale, hale, hale, Be hungry... be healthy... be hungrier... be blessed, be
ANOREXIA!!

May Jesus ( Prayerfully in the infinite power and might of the Holy Spirit )
{*filter*} you up the ass!!

--
Bubba Do Wah Ditty



Quote:

>> Scientists Identify Gene Responsible for Statin-Induced Muscle Pain



Mon, 17 May 2010 23:29:52 GMT
 
 [ 3 post ] 

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