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ACAD9 treatment with bezafibrate and nicotinamide riboside temporarily stabilizes cardiomyopathy and lactic acidosis.
Van Hove, Johan L K; Friederich, Marisa W; Hock, Daniella H; Stroud, David A; Caruana, Nikeisha J; Christians, Uwe; Schniedewind, Björn; Michel, Cole R; Reisdorph, Richard; Lopez Gonzalez, Edwin D J; Brenner, Charles; Donovan, Tonia E; Lee, Jessica C; Chatfield, Kathryn C; Larson, Austin A; Baker, Peter R; McCandless, Shawn E; Moore Burk, Meghan F.
Afiliação
  • Van Hove JLK; Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado, Aurora, CO 80045, USA; Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, CO 80045, USA. Electronic address: Johan.Vanhove@childrenscolorado.org.
  • Friederich MW; Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado, Aurora, CO 80045, USA; Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, CO 80045, USA.
  • Hock DH; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3052, Australia; Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia; Victorian Clinical Genetics Servi
  • Stroud DA; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3052, Australia; Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria 3052, Australia; Victorian Clinical Genetics Servi
  • Caruana NJ; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3052, Australia.
  • Christians U; iC42 Clinical Research and Development, Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Schniedewind B; iC42 Clinical Research and Development, Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Michel CR; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Reisdorph R; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
  • Lopez Gonzalez EDJ; Department of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
  • Brenner C; Department of Diabetes and Cancer Metabolism, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
  • Donovan TE; Department of Pathology and Laboratory Medicine, Children's Hospital Colorado, Aurora, CO 80045, USA.
  • Lee JC; Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado, Aurora, CO 80045, USA.
  • Chatfield KC; Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado, Aurora, CO 80045, USA; Department of Pediatrics, Section of Cardiology, University of Colorado, Aurora, CO, USA.
  • Larson AA; Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado, Aurora, CO 80045, USA.
  • Baker PR; Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado, Aurora, CO 80045, USA.
  • McCandless SE; Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado, Aurora, CO 80045, USA.
  • Moore Burk MF; Department of Physical Medicine and Rehabilitation, Children's Hospital Colorado, 13121 East 16(th) Avenue, Aurora, CO, USA.
Mitochondrion ; 78: 101905, 2024 May 24.
Article em En | MEDLINE | ID: mdl-38797357
ABSTRACT
Pathogenic ACAD9 variants cause complex I deficiency. Patients presenting in infancy unresponsive to riboflavin have high mortality. A six-month-old infant presented with riboflavin unresponsive lactic acidosis and life-threatening cardiomyopathy. Treatment with high dose bezafibrate and nicotinamide riboside resulted in marked clinical improvement including reduced lactate and NT-pro-brain type natriuretic peptide levels, with stabilized echocardiographic measures. After a long stable period, the child succumbed from cardiac failure with infection at 10.5 months. Therapy was well tolerated. Peak bezafibrate levels exceeded its EC50. The clinical improvement with this treatment illustrates its potential, but weak PPAR agonist activity of bezafibrate limited its efficacy.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article