Abstract
Background2-Hydroxybenzylamine (2-HOBA) is a selective scavenger of dicarbonyl electrophiles that protects proteins and lipids from being modified by these electrophiles. It is currently being developed for use as a nutritional supplement to help maintain good health and protect against the development of conditions associated with dicarbonyl electrophile formation, such as the cognitive decline associated with Mild Cognitive Impairment and Alzheimer’s disease.MethodsIn this first-in-human study, the safety, tolerability, and pharmacokinetics of six ascending single oral doses of 2-HOBA acetate were tested in eighteen healthy human volunteers.ResultsReported adverse events were mild and considered unlikely to be related to 2-HOBA. There were no clinically significant changes in vital signs, ECG recordings, or clinical laboratory parameters. 2-HOBA was fairly rapidly absorbed, with a tmax of 1–2 h, and eliminated, with a t1/2 of approximately 2 h. Both tmax and t1/2 were independent of dose level, while Cmax and AUC increased proportionally with dose level.Conclusions2-HOBA acetate was safe and well-tolerated at doses up to 825 mg in healthy human volunteers, positioning it as a good candidate for continued development as a nutritional supplement.Trial registrationThis study is registered at ClinicalTrials.gov (NCT03176940).
Highlights
Inflammation and oxidative stress, which have been implicated as potential mediators in the development and progression of many conditions, result in the formation of extremely reactive dicarbonyl electrophiles
Dicarbonyl electrophiles can be neutralized by a novel class of scavenger molecules [9]
(2019) 20:1 (2-HOBA), reacts substantially faster with these dicarbonyls than does lysine, preventing dicarbonly-associated protein modifications. 2-HOBA, which is naturally found in buckwheat [10], is orally available [11] and crosses the blood brain barrier, resulting in brain 2-HOBA levels approximately twice as high as plasma levels [11]
Summary
Inflammation and oxidative stress, which have been implicated as potential mediators in the development and progression of many conditions, result in the formation of extremely reactive dicarbonyl electrophiles. These dicarbonyls react with lysine residues to form protein adducts that can alter the function and interactions of various cellular proteins [1, 2]. The objective of the present investigation was to perform the initial evaluation of 2-HOBA acetate in humans. This first-in-human study assessed the safety, tolerability, and pharmacokinetics of single ascending doses of 2-HOBA acetate in healthy humans
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