Objective: To present the detailed clinical features of a patient with familial MSA carrying compound heterozygous COQ2 mutations and report the outcome of a high-dose ubiquinol supplementation to this patient.

Background: We have revealed biallelic mutations in COQ2 in two of the six multiplex Japanese families with MSA. Decreased biosynthesis of CoQ10 as a result of mutations in COQ2 is considered to underlie the increased risk for developing MSA, raising the possibility that high-dose CoQ10 supplementation is effective to retard disease progression of MSA, in particular, for patients with COQ2 mutations.

Methods: An open-label dose escalation trial for this patient with familial MSA with compound heterozygous COQ2 mutations (R387X/V393A) was designed to evaluate the safety and tolerability of high-dose ubiquinol (from 600 mg/day to 1,200 mg/day), to assess pharmacokinetics, and to evaluate clinical outcome based on the clinical rating scales including Barthel index, SARA, ICARS, and UMSARS. PET was carried out to measure the cerebral blood flow and the cerebral metabolic rate of oxygen (CMRO2).

Results: A high-dose ubiquinol supplementation substantially increased total CoQ10 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 three years. The CMRO2 measured by 15O2 PET, however, increased after administration of ubiquinol, suggesting that ubiquinol can improve mitochondrial oxidative metabolism in the brain. The mean changes from baseline of CMRO2 in 7 regions of interest was 30.0% (range, 18.8‒52.2%).

Conclusions: This study demonstrates that high-dose ubiquinol supplementation (up to 1,200 mg/day) is tolerable and improves cerebral mitochondrial oxidative metabolism, which may alter the natural history of MSA progression especially when applied in the early phase of MSA in patients with genetic defects in the CoQ10 biosynthetic pathway. Further clinical trials including administration of ubiquinol to MSA patients carrying heterozygous COQ2 mutations as well as to those without mutations in COQ2 are warranted. Prospective randomized controlled trials will be undertaken to further extend these initial promising observations.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/three-year-follow-up-of-high-dose-ubiquinol-supplementation-in-a-case-of-familial-multiple-system-atrophy-with-compound-heterozygous-coq2-mutations/