Towards a new non-invasive diagnostic tool for complex III deficiency

Statins are the worlds most prescribed cholesterol-lowering drugs and are highly effective in reducing the risk of cardiovascular disease. Some of the statin-users experience muscle pains but the incidence is debated and so are the complaints, which are by many attributed to a nocebo (opposite of placebo) effect. Research of the department of Pharmacology and Toxicology has previously shown that statins inhibit mitochondrial complex III (CIII) and that CIII activity is inversely correlated with muscle pain intensity in symptomatic statin users.

As muscle pain is a common complaint of statin users, it is crucial to distinguish it from other causes of myalgia to prevent unnecessary cessation of drug therapy. Diagnosing CIII inhibition currently requires muscle biopsies, which are invasive and not practical for routine testing. In a collaborative study with the Departments of Pharmacy, division Pharmacology and Toxicology, Physiology and Cardiothoracic Surgery, a spectrophotometric method was developed to determine CIII catalytic activities using patient-friendly buccal swabs, which was validated in a cohort of statin and non-statin users. The data indicate that CIII can be reliably measured in buccal swabs, as evidenced by reproducible results above the detection limit. Further validation on a larger scale is required for implementation as a reliable dipstick assay in the clinical setting.

Publication

Scientific Reports. Somers T, Allard NAE, Siddiqi S, Janssen MCM, Hopman MTE, Morshuis WJ, Russel FGM, Timmers S, Schirris TJJ. Mitochondrial complex III activity: from invasive muscle biopsies to patient-friendly buccal swab analysis.