This is a study from Japan. Ubiquinol plays an essential role in mitochondrial electron transport. With ATH434 in the phase 2 study we wait for a stronger effect ( regaining motor activity?) as was demonstrated in the animal models. It may be that ubiquinol will become one drug in treating MSA, hopefully combined with ATH434.

EClinicalMedicine

. 2023 Apr 14;59:101920.

doi: 10.1016/j.eclinm.2023.101920. eCollection 2023 May.

High-dose ubiquinol supplementation in multiple-system atrophy: a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial

Jun Mitsui ¹, Takashi Matsukawa ¹, Yukari Uemura ², Takuya Kawahara ³, Ayaka Chikada ⁴, Kristine Joyce L Porto ¹, Hiroya Naruse ⁴, Masaki Tanaka ⁵, Hiroyuki Ishiura ⁴, Tatsushi Toda ⁴, Haruko Kuzuyama ³, Mari Hirano ³, Ikue Wada ³, Toshio Ga ³, Takashi Moritoyo ³, Yuji Takahashi ⁶, Hidehiro Mizusawa ⁶, Kinya Ishikawa ⁷, Takanori Yokota ⁷, Satoshi Kuwabara ⁸, Nobukatsu Sawamoto ⁹, Ryosuke Takahashi ⁹, Koji Abe ¹⁰, Tomohiko Ishihara ¹¹, Osamu Onodera ¹¹, Dai Matsuse ¹², Ryo Yamasaki ¹², Jun-Ichi Kira ¹², Masahisa Katsuno ¹³, Ritsuko Hanajima ¹⁴, Katsuhisa Ogata ¹⁵, Hiroshi Takashima ¹⁶, Masaaki Matsushima ¹⁷, Ichiro Yabe ¹⁷, Hidenao Sasaki ¹⁷, Shoji Tsuji ^{1 5}

Affiliations expand

• PMID: 37256098

PMCID: PMC10225719 DOI: 10.1016/j.eclinm.2023.101920Free PMC article

Abstract

Background: Functionally impaired variants of COQ2, encoding an enzyme in biosynthesis of coenzyme Q10 (CoQ10), were found in familial multiple system atrophy (MSA) and V393A in COQ2 is associated with sporadic MSA. Furthermore, reduced levels of CoQ10 have been demonstrated in MSA patients.

Methods: This study was a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial. Patients with MSA were randomly assigned (1:1) to either ubiquinol (1500 mg/day) or placebo. The primary efficacy outcome was the change in the unified multiple system atrophy rating scale (UMSARS) part 2 at 48 weeks. Efficacy was assessed in all patients who completed at least one efficacy assessment (full analysis set). Safety analyses included patients who completed at least one dose of investigational drug. This trial is registered with UMIN-CTR (UMIN000031771), where the drug name of MSA-01 was used to designate ubiquinol.

Findings: Between June 26, 2018, and May 27, 2019, 139 patients were enrolled and randomly assigned to the ubiquinol group (n = 69) or the placebo group (n = 70). A total of 131 patients were included in the full analysis set (63 in the ubiquinol group; 68 in the placebo group). This study met the primary efficacy outcome (least square mean difference in UMSARS part 2 score (-1.7 [95% CI, -3.2 to -0.2]; P = 0.023)). The ubiquinol group also showed better secondary efficacy outcomes (Barthel index, Scale for the Assessment and Rating of Ataxia, and time required to walk 10 m). Rates of adverse events potentially related to the investigational drug were comparable between ubiquinol (n = 15 [23.8%]) and placebo (n = 21 [30.9%]).

Interpretation: High-dose ubiquinol was well-tolerated and led to a significantly smaller decline of UMSARS part 2 score compared with placebo.