Safety and target engagement profile of two oxaloacetate doses in Alzheimer's patients.
Aged
Aged, 80 and over
Alzheimer Disease
/ drug therapy
Brain
/ drug effects
Cognition
/ drug effects
Dose-Response Relationship, Drug
Energy Metabolism
/ drug effects
Female
Fluorodeoxyglucose F18
Glucose
/ metabolism
Glutathione
/ metabolism
Humans
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Male
Middle Aged
Neuropsychological Tests
Oxaloacetic Acid
/ administration & dosage
Positron-Emission Tomography
Radiopharmaceuticals
Alzheimer's disease
bioenergetics
metabolism
oxaloacetate
safety
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
07
02
2020
revised:
19
06
2020
accepted:
28
06
2020
pubmed:
28
7
2020
medline:
26
10
2021
entrez:
28
7
2020
Statut:
ppublish
Résumé
Brain bioenergetics are defective in Alzheimer's disease (AD). Preclinical studies find oxaloacetate (OAA) enhances bioenergetics, but human safety and target engagement data are lacking. We orally administered 500 or 1000 mg OAA, twice daily for 1 month, to AD participants (n = 15 each group) and monitored safety and tolerability. To assess brain metabolism engagement, we performed fluorodeoxyglucose positron emission tomography (FDG PET) and magnetic resonance spectroscopy before and after the intervention. We also assessed pharmacokinetics and cognitive performance. Both doses were safe and tolerated. Compared to the lower dose, the higher dose benefited FDG PET glucose uptake across multiple brain regions (P < .05), and the higher dose increased parietal and frontoparietal glutathione (P < .05). We did not demonstrate consistent blood level changes and cognitive scores did not improve. 1000 mg OAA, taken twice daily for 1 month, is safe in AD patients and engages brain energy metabolism.
Identifiants
pubmed: 32715609
doi: 10.1002/alz.12156
pmc: PMC8084114
mid: NIHMS1693488
doi:
Substances chimiques
Radiopharmaceuticals
0
Fluorodeoxyglucose F18
0Z5B2CJX4D
Oxaloacetic Acid
2F399MM81J
Glutathione
GAN16C9B8O
Glucose
IY9XDZ35W2
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7-17Subventions
Organisme : NCI NIH HHS
ID : P30 CA168524
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG035982
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072973
Pays : United States
Organisme : University of Kansas Alzheimer's Disease Center
ID : P30AG035982
Pays : International
Organisme : University of Kansas Cancer Center
ID : P30CA168524
Pays : International
Informations de copyright
© 2020 the Alzheimer's Association.
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