Coenzyme Q ₁₀ reverses pathological phenotype and reduces apoptosis in familial CoQ ₁₀ deficiency

Abstract

Two brothers with myopathic coenzyme Q10 (CoQ10) deficiency responded dramatically to CoQ10 supplementation. Muscle biopsies before therapy showed ragged-red fibers, lipid storage, and complex I + III and II + III deficiency. Approximately 30% of myofibers had multiple features of apoptosis. After 8 months of treatment, excessive lipid storage resolved, CoQ10 level normalized, mitochondrial enzymes increased, and proportion of fibers with TUNEL-positive nuclei decreased to 10%. The authors conclude that muscle CoQ10 deficiency can be corrected by supplementation of CoQ10, which appears to stimulate mitochondrial proliferation and to prevent apoptosis.

Mutations in coenzyme Q10 biosynthetic genes

“…It was concluded that the primary defect in this family probably involved a tissuespecific isozyme in the CoQ 10 synthetic pathway of muscle and brain. Although this study was published in a high-profile journal, the report was followed by a remarkably long silence: the next publications on patients with the same clinical triad (mitochondrial myopathy, recurrent myoglobinuria, and CNS signs) and muscle CoQ 10 deficiency appeared 8 and 11 years later (2,3). Notably, all patients improved remarkably with oral CoQ 10 supplementation.…”

Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders

“…CoQ 10 also plays a critical role in antioxidant defenses (1). Primary CoQ 10 deficiency is a rare, but possibly treatable, autosomal recessive condition with 3 major clinical presentations: (a) an encephalomyopathic form, characterized by exercise intolerance, mitochondrial myopathy, myoglobinuria, epilepsy, and ataxia (2)(3)(4)(5); (b) a generalized infantile variant with severe encephalopathy and renal disease (6)(7)(8); and (c) an ataxic form, dominated by ataxia, seizures, cerebral atrophy, and/or anomalies of the basal ganglia (9,10). Recurrence of the disease and/or consanguinity of the parents in some reported families suggest an autosomal recessive mode of inheritance.…”

How Can We Treat Mitochondrial Encephalomyopathies? Approaches to Therapy

“…Supplementation with CoQ10 resulted in clinical improvement in several early reports, with the primary molecular cause not known. 53,54 Muscle strength returned to normal in two brothers described by Di Giovanni et al 55 in 2001. Furthermore, a repeated muscle biopsy after 8 months of therapy showed improvement in the histological parameters, normalization of CoQ10 levels and reduction in the proportion of fibers undergoing apoptosis.…”