Posiphen as a candidate drug to lower CSF amyloid precursor protein, amyloid-β peptide and τ levels: target engagement, tolerability and pharmacokinetics in humans

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 83; no. 9; pp. 894 - 902
• Main Authors: Maccecchini, Maria L, Chang, Mee Young, Pan, Catherine, John, Varghese, Zetterberg, Henrik, Greig, Nigel H
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.09.2012; BMJ Publishing Group; BMJ Group
• Series: Research paper
• Subjects: Alzheimer's disease; amyloid; Amyloid beta-Peptides - cerebrospinal fluid; Amyloid beta-Protein Precursor - cerebrospinal fluid; amyloid precursor protein; amyloid-β peptide; Animals; B12 deficiency; Biological and medical sciences; Cognitive Dysfunction - blood; Cognitive Dysfunction - cerebrospinal fluid; Cognitive Dysfunction - drug therapy; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dose-Response Relationship, Drug; Double-Blind Method; Female; genetics; head injury; Humans; Inflammation Mediators - cerebrospinal fluid; inflammatory markers; Male; Medical sciences; mild cognitive impairment; neurochemistry; Neurodegeneration; Neurology; Parkinson's disease; Peptide Fragments - cerebrospinal fluid; Physostigmine - adverse effects; Physostigmine - analogs & derivatives; Physostigmine - pharmacokinetics; Physostigmine - pharmacology; Posiphen; Rats; Rats, Inbred F344; tau Proteins - cerebrospinal fluid; Human; Nervous system diseases; Peptides; β Amyloid protein; Cerebrospinal fluid; Pharmacokinetics; Amyloid precursor protein

AimA first in human study to evaluate tolerability and pharmacokinetics followed by an early proof of mechanism (POM) study to determine whether the small orally, available molecule, Posiphen tartrate (Posiphen), lowers secreted (s) amyloid-β precursor protein (APP) α and -β, amyloid-β peptide (Aβ),...