Navigation Links
Scientists identify gene responsible for statin-induced muscle pain
Date:11/27/2007

BOSTON Statins, the popular class of drugs 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 studys 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. And, 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.


'/>"/>

Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

Related medicine news :

1. New prion protein discovered by Canadian scientists may offer insight into mad cow disease
2. Scientists Probe Sepsis Deadly Secrets
3. Scientists puzzled by severe allergic reaction to cancer drug in the middle Southern US
4. Scientists Develop Natural Protection for Stored Foods
5. Scientists detect presence of marburg virus in african fruit bats
6. Scientists Spot Brains Free Will Center
7. Scientists ID Likely Culprit in Popcorn Lung
8. Scientists explain how insulin secreting cells maintain their glucose sensitivity
9. Scripps Research scientists shed new light on how antibodies fight HIV
10. Scientists, physicians present latest findings in personalized cancer treatment and prevention
11. Scientists demonstate link between genetic variant and effectiveness of smoking cessation meds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/29/2017)... ... March 29, 2017 , ... Full Contact K9, an Atlanta-based dog ... Protect Law that assists dog owners in creating legally-enforceable pet trusts for their ... the natural next step to protect their new companion. Says Evan Dunbar, CEO of ...
(Date:3/29/2017)... ... ... CHARM CITY RUN WELCOMES MERCY MEDICAL CENTER AS , BALTIMORE WOMEN’S CLASSIC TITLE ... the official title sponsor of the Baltimore Women’s Classic, the largest all women’s 5K ... walk or run the course around the Baltimore Inner Harbor. Mercy has been the ...
(Date:3/29/2017)... ... March 30, 2017 , ... Sublime Naturals and its founder, Kathy Heshelow, ... Spice", it has been used for thousands of years. , "The West has caught ... of " Turmeric: How to Use it For Your Wellness. Overcome Inflammation, Enemy of ...
(Date:3/29/2017)... ... March 29, 2017 , ... Wells Pharmacy Network, ... prescribers at the upcoming World Congress, in Hollywood Florida April 6-8, 2017. , ... as the visionary leader in the training of physicians, scientists, and members of ...
(Date:3/29/2017)... ... March 29, 2017 , ... The Wall Centre Dental team ... patients from Burnaby, BC. Patients in need of experienced orthodontics, laser dentistry, porcelain ... the esteemed team at Wall Centre Dental. Drs. Parviz Roshan, Siamak Tehrani, Milton ...
Breaking Medicine News(10 mins):
(Date:3/29/2017)... , March 29, 2017 Avelas Biosciences, Inc., a clinical ... through treatment, today announced that Carmine N. Stengone , president ... at the Needham & Company 16 th Annual Healthcare Conference ... PDT) at the Westin Grand Central Hotel in New ... ...
(Date:3/29/2017)... , March 29, 2017 Today, CVS Health ... Kim Reynolds , Department of Public Health Director ... Steve Lukan in announcing the availability of the ... Pharmacy locations in Iowa.  CVS Health has established a standing ... allows CVS Pharmacy to expand access to the medication in ...
(Date:3/29/2017)... CREEK, Calif. , Mar 29, 2017 /PRNewswire/ ... cervical-fusion technology, announced the addition of two industry ... Lynch has joined the company to lead ... assuming International leadership.  Together, Mr. Lynch and Mr. ... experience.  Mr. Lynch joins the ...
Breaking Medicine Technology: