The cerebellar bioenergetic state predicts treatment response in COQ8A-related ataxia

J Prasuhn; M Göttlich; B Ebeling; C Bodemann; S Großer; I Wellach; K Reuther; H Hanssen; N Brüggemann

doi:10.1016/j.parkreldis.2022.05.008

The cerebellar bioenergetic state predicts treatment response in COQ8A-related ataxia

Parkinsonism Relat Disord. 2022 Jun:99:91-95. doi: 10.1016/j.parkreldis.2022.05.008. Epub 2022 May 19.

Authors

J Prasuhn¹, M Göttlich², B Ebeling³, C Bodemann⁴, S Großer⁵, I Wellach⁶, K Reuther⁷, H Hanssen⁸, N Brüggemann⁹

Affiliations

¹ Institute of Neurogenetics, University of Lübeck, Marie-Curie-Straße 1, 23562, Lübeck, Germany; Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany; Center for Brain, Behavior, and Metabolism, University of Lübeck, Marie-Curie-Straße 2, 23562, Lübeck, Germany. Electronic address: jannik.prasuhn@neuro.uni-luebeck.de.
² Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany; Center for Brain, Behavior, and Metabolism, University of Lübeck, Marie-Curie-Straße 2, 23562, Lübeck, Germany. Electronic address: martin.goettlich@neuro.uni-luebeck.de.
³ Institute of Neurogenetics, University of Lübeck, Marie-Curie-Straße 1, 23562, Lübeck, Germany; Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany; Center for Brain, Behavior, and Metabolism, University of Lübeck, Marie-Curie-Straße 2, 23562, Lübeck, Germany. Electronic address: britt.ebeling@neuro.uni-luebeck.de.
⁴ Institute of Neurogenetics, University of Lübeck, Marie-Curie-Straße 1, 23562, Lübeck, Germany; Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany; Center for Brain, Behavior, and Metabolism, University of Lübeck, Marie-Curie-Straße 2, 23562, Lübeck, Germany. Electronic address: christina.bodemann@neuro.uni-luebeck.de.
⁵ Institute of Neurogenetics, University of Lübeck, Marie-Curie-Straße 1, 23562, Lübeck, Germany; Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany; Center for Brain, Behavior, and Metabolism, University of Lübeck, Marie-Curie-Straße 2, 23562, Lübeck, Germany. Electronic address: sinja.grosser@neuro.uni-luebeck.de.
⁶ Department of Neurology, Ev. Amalie, Sieveking Hospital, Haselkamp 33, 22359, Hamburg, Germany. Electronic address: ingmar.wellach@immanuelalbertinen.de.
⁷ Institute of Neurogenetics, University of Lübeck, Marie-Curie-Straße 1, 23562, Lübeck, Germany; Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany; Center for Brain, Behavior, and Metabolism, University of Lübeck, Marie-Curie-Straße 2, 23562, Lübeck, Germany. Electronic address: katharina.reuther@neuro.uni-luebeck.de.
⁸ Institute of Neurogenetics, University of Lübeck, Marie-Curie-Straße 1, 23562, Lübeck, Germany; Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany; Center for Brain, Behavior, and Metabolism, University of Lübeck, Marie-Curie-Straße 2, 23562, Lübeck, Germany. Electronic address: henrike.hanssen@neuro.uni-luebeck.de.
⁹ Institute of Neurogenetics, University of Lübeck, Marie-Curie-Straße 1, 23562, Lübeck, Germany; Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany; Center for Brain, Behavior, and Metabolism, University of Lübeck, Marie-Curie-Straße 2, 23562, Lübeck, Germany. Electronic address: norbert.brueggemann@neuro.uni-luebeck.de.

PMID: 35642996
DOI: 10.1016/j.parkreldis.2022.05.008

Abstract

Introduction: Primary coenzyme Q10 (CoQ10) deficiency, a recessive disorder associated with various defects of CoQ10 biosynthesis and widely varying clinical presentation, is customarily managed by oral Q10 supplementation but the benefit is debated.

Methods: To address this question, we mapped individual responses in two patients with COQ8A-related ataxia following coenzyme Q10 supplementation using noninvasive imaging. Metabolic ³¹phosphorus magnetic resonance spectroscopy imaging (³¹P-MRSI) and volumetric cerebellar neuroimaging were performed to quantify the individual treatment response in two patients with COQ8A-related ataxia, each compared with eight age- and gender-matched healthy control subjects.

Results: Post-treatment change in energy metabolite levels differed in the two patients, with higher energy levels and improved dysarthria and leg coordination in one, and decreased energy levels without clinical benefit in the other.

Conclusions: Our results suggest that the cerebellar bioenergetic state may predict treatment response in COQ8A-related ataxia and highlight the potential of pathophysiology-orientated neuroimaging evidence to inform treatment decisions.

Keywords: ADCK3; Ataxia; COQ8A; Magnetic resonance spectroscopy; Mitochondria; Molecular imaging; Primary coenzyme Q10 deficiencies.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ataxia / complications
Ataxia / diagnostic imaging
Ataxia / drug therapy
Cerebellar Ataxia* / complications
Cerebellar Ataxia* / diagnostic imaging
Cerebellar Ataxia* / drug therapy
Energy Metabolism
Humans
Mitochondrial Diseases* / complications
Muscle Weakness / complications
Ubiquinone / deficiency
Ubiquinone / therapeutic use

Substances

Ubiquinone

Supplementary concepts

Coenzyme Q10 Deficiency