【摘 要】
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Background: Posiphen is in clinical development as an oral treatment for Alzheimers disease (AD).In cell cultures, normal, transgenic and trisomic mice Posiphen reduces the rate of synthesis of amyloi
【机 构】
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QR Pharma, Inc.USA
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Background: Posiphen is in clinical development as an oral treatment for Alzheimers disease (AD).In cell cultures, normal, transgenic and trisomic mice Posiphen reduces the rate of synthesis of amyloid-precursor protein (APP) and, thereby, lowers levels of A and potentially other toxic peptides generated from APP processing.We conducted an exploratory study in patients with amnestic mild cognitive impairment (MCI) to measure the levels of Posiphen and its metabolites in CSF and plasma and correlate these levels with the associated pharmacodynarnic and disease related biomarkers.Methods: Five (5) amnestie MCI patients received Posiphen at 240 rag/day for 10 days (4×60 mg was confirmed as well tolerated in a separate multiple dose safety study in elderly healthy volunteers).Serial CSF samples were collected via indwelling lumbar catheter for 12 hours one day before the start of dosing and over 12 hours immediately after the last dose on day 10.Sampling times for plasma and CSF were matched.CSF and plasma/serum samples were analyzed for-PK: Posiphen and the primary metabolites: N 1-norPositphen, N8-norPosiphen, N 1, N8-norPosiphen; -PD: soluble α and βAPP, Aβ 40/42, AChEI/BChEI, Tau/phospho-Tau, other potential AD associated markers.Results: 10 days of Posiphen administration results in lowering levels of sAPP alpha and beta as well as Tau and phospho-Tau by 40% back to the levels measured in healthy volunteers.Posiphen does not just normalize CSF levels of AD associated biomarkers, but also lowers complement factors and increases neurotrophic factors, leading to a CNS profile that closely resembles the profile seen in healthy, normal volunteers.
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