Rationale: The aim of this work is to show how statins (which are used to prevent and treat cardiovascular disease) cause skeletal muscle pain and weakness (myopathy). This is a major concern as myopathy is seen in up to one quarter of the 7 million people in the UK who take statins and it is the main reason that people stop taking these life-saving drugs. Myopathy can also stop people exercising (which is additionally bad for health). Our research will identify the mechanism of myopathy and this will allow the development of new treatments to be taken along with statins to prevent their harmful effects on skeletal muscle. This will improve statin use and so improve cardiovascular health.
Plan of work: We will treat rats with statins over a 4 week time period. At the end of the experiment, rats will be humanely killed and samples of skeletal (and cardiac muscle) taken for many different types of analysis of muscle function, structure and biochemistry.
Animal welfare: All animals will be very carefully monitored and if there is any evidence of more than mild discomfort, the study will be terminated.
Reduction/Refinement/Replacement: We do have a limited supply of skeletal muscle from statin-treated patients which we can use for some experiments, however it is difficult to properly test the mechanism of myopathy with these samples because people who take statins may have diseases or will be taking other medication which complicates the interpretation of results. Treatment of living animals (rats) with statins is required to allow us to model the situation of people taking statins. Use of human cultured skeletal muscle cell lines in vitro is not appropriate for the current project because statins must be chronically administered in living animals in order to mimic the clinical situation. We have performed calculations that tell us the minimum number of animals required in order to be able to test our hypothesis. For every animal we will derive the maximum amount of data that we can from it. We will also share tissue from these animals with other scientists who are interested in statin effects on e.g. the brain/nervous system.
Implications: It is essential to find out why statin myopathy arises so this can be treated as there are no cost-effective alternatives to statin treatment in those at risk of cardiovascular disease.
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