Safety and target engagement profile of two oxaloacetate doses in Alzheimer's patients: Brain energy rescue interventions to treat or delay Alzheimer's disease. (7th December 2020)

• Record Type: Journal Article
• Authors: Swerdlow, Russell H
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 10
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.037962
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: 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.