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Safety and target engagement profile of two oxaloacetate doses in Alzheimer’s patients
Author(s) -
Swerdlow Russell H
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.037962
Subject(s) - tolerability , medicine , positron emission tomography , pharmacokinetics , bioenergetics , neurodegeneration , citrate synthase , glutathione , pharmacology , psychology , adverse effect , disease , nuclear medicine , chemistry , biochemistry , mitochondrion , enzyme
Background 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. Method 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 (MRS) prior to and after the intervention. We also screened pharmacokinetics and cognitive performance. Result Both doses were well‐tolerated. Compared to the 500 mg dose, the 1000 mg dose benefited default mode network glucose utilization on FDG PET (p<0.05), and the 1000 mg dose increased frontoparietal glutathione (p<0.05). We did not demonstrate consistent changes in blood levels, and cognitive scores did not improve. Conclusion 1000 mg OAA, taken twice daily for 1 month, is safe in AD patients and engages brain energy metabolism.