Three-Year Follow-Up of High-Dose Ubiquinol Supplementation in a Case of Familial Multiple System Atrophy with Compound Heterozygous COQ2 Mutations

Abstract

We report a 3-year follow-up of high-dose ubiquinol supplementation in a case of familial multiple system atrophy (MSA) with compound heterozygous nonsense (R387X) and missense (V393A) mutations in COQ2. A high-dose ubiquinol supplementation substantially increased total coenzyme Q10 levels in cerebrospinal fluid as well as in plasma. The patient was at the advanced stage of MSA, and the various scores of clinical rating scales remained stable without changes during the 3 years. The cerebral metabolic ratio of oxygen measured by 15O2 PET, however, increased by approximately 30% after administration of ubiquinol, suggesting that ubiquinol can improve mitochondrial oxidative metabolism in the brain. It also suggests the therapeutic potential of ubiquinol for patients with MSA with COQ2 mutations. Further clinical trials of administration of high-dose ubiquinol to MSA patients are warranted.

The pathogenesis linked to coenzyme Q10 insufficiency in iPSC-derived neurons from patients with multiple-system atrophy

“…We established iPSCs from two patients (MSA_A and MSA_B) who were clinically diagnosed with cerebellar type of MSA. MSA_A, an affected member of a previously described Japanese multiplex family with MSA 12 , 25 , was 61-year-old male. He was observed to have staggering gait, dysarthria, hypotension and erectile dysfunction at the age of 44 years.…”

Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide

“…CoQ is a lipophilic antioxidant that crosses the blood-brain barrier [20,26]. Exogenous CoQ is first accumulated in the endolysosomal compartment, and then rapidly becomes incorporated to mitochondria-associated membranes and mitochondria [26].…”

“…In this work, we explore the role of coenzyme Q 10 (CoQ) in the mechanisms evoking radioresistance using two human GBM cell lines, U251 and T98, compared to non-transformed astrocytes C8D1A. CoQ is a lipophilic antioxidant that crosses the blood-brain barrier [20]. Besides, it is a component of the mitochondrial electron transport chain (ETC) that dampens the O 2 ÅÀ generated by complex I in dystrophic mitochondria [12].…”

Current Symptomatic and Disease-Modifying Treatments in Multiple System Atrophy

“…This raises the question whether supplementation of coenzyme Q10 might be a well-tailored substitution in MSA patients carrying COQ2 mutations. A first case report in a COQ2 deficient patient provided a first hint that high-dose treatment with ubiquinol, the reduced form of coenzyme Q10, might be efficacious [149]. Currently, a randomized, double-blind, placebo-controlled phase 1 study is investigating safety and pharmacokinetics of the reduced form of coenzyme Q10 (MSA-01) in healthy male subjects [150].…”