Mitochondrial medicine therapies: rationale, evidence, and dosing guidelines.
Journal
Current opinion in pediatrics
ISSN: 1531-698X
Titre abrégé: Curr Opin Pediatr
Pays: United States
ID NLM: 9000850
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
pubmed:
27
10
2020
medline:
17
2
2021
entrez:
26
10
2020
Statut:
ppublish
Résumé
Primary mitochondrial disease is a highly heterogeneous but collectively common inherited metabolic disorder, affecting at least one in 4300 individuals. Therapeutic management of mitochondrial disease typically involves empiric prescription of enzymatic cofactors, antioxidants, and amino acid and other nutrient supplements, based on biochemical reasoning, historical experience, and consensus expert opinion. As the field continues to rapidly advance, we review here the preclinical and clinical evidence, and specific dosing guidelines, for common mitochondrial medicine therapies to guide practitioners in their prescribing practices. Since publication of Mitochondrial Medicine Society guidelines for mitochondrial medicine therapies management in 2009, data has emerged to support consideration for using additional therapeutic agents and discontinuation of several previously used agents. Preclinical animal modeling data have indicated a lack of efficacy for vitamin C as an antioxidant for primary mitochondrial disease, but provided strong evidence for vitamin E and N-acetylcysteine. Clinical data have suggested L-carnitine may accelerate atherosclerotic disease. Long-term follow up on L-arginine use as prophylaxis against or acute treatment for metabolic strokes has provided more data supporting its clinical use in individuals with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome and Leigh syndrome. Further, several precision therapies have been developed for specific molecular causes and/or shared clinical phenotypes of primary mitochondrial disease. We provide a comprehensive update on mitochondrial medicine therapies based on current evidence and our single-center clinical experience to support or refute their use, and provide detailed dosing guidelines, for the clinical management of mitochondrial disease. The overarching goal of empiric mitochondrial medicines is to utilize therapies with favorable benefit-to-risk profiles that may stabilize and enhance residual metabolic function to improve cellular resiliency and slow clinical disease progression and/or prevent acute decompensation.
Identifiants
pubmed: 33105273
doi: 10.1097/MOP.0000000000000954
pmc: PMC7774245
mid: NIHMS1651614
pii: 00008480-202012000-00002
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
707-718Subventions
Organisme : NIDDK NIH HHS
ID : K08 DK113250
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM134863
Pays : United States
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