Positron emission tomography measurement of brain MAO-B inhibition in patients with Alzheimer’s disease and elderly controls after oral administration of sembragilineReport as inadecuate




Positron emission tomography measurement of brain MAO-B inhibition in patients with Alzheimer’s disease and elderly controls after oral administration of sembragiline - Download this document for free, or read online. Document in PDF available to download.

European Journal of Nuclear Medicine and Molecular Imaging

, Volume 44, Issue 3, pp 382–391

First Online: 16 September 2016Received: 01 April 2016Accepted: 29 August 2016DOI: 10.1007-s00259-016-3510-6

Cite this article as: Sturm, S., Forsberg, A., Nave, S. et al. Eur J Nucl Med Mol Imaging 2017 44: 382. doi:10.1007-s00259-016-3510-6

Abstract

PurposeIn Alzheimer’s disease AD, increased metabolism of monoamines by monoamine oxidase type B MAO-B leads to the production of toxic reactive oxygen species ROS, which are thought to contribute to disease pathogenesis. Inhibition of the MAO-B enzyme may restore brain levels of monoaminergic neurotransmitters, reduce the formation of toxic ROS and reduce neuroinflammation reactive astrocytosis, potentially leading to neuroprotection. Sembragiline also referred as RO4602522, RG1577 and EVT 302 in previous communications is a potent, selective and reversible inhibitor of MAO-B developed as a potential treatment for AD.

MethodsThis study assessed the relationship between plasma concentration of sembragiline and brain MAO-B inhibition in patients with AD and in healthy elderly control EC subjects. Positron emission tomography PET scans using C-L-deprenyl-D2 radiotracer were performed in ten patients with AD and six EC subjects, who received sembragiline each day for 6–15 days.

ResultsAt steady state, the relationship between sembragiline plasma concentration and MAO-B inhibition resulted in an Emax of ∼80–90 % across brain regions of interest and in an EC50 of 1–2 ng-mL. Data in patients with AD and EC subjects showed that near-maximal inhibition of brain MAO-B was achieved with 1 mg sembragiline daily, regardless of the population, whereas lower doses resulted in lower and variable brain MAO-B inhibition.

ConclusionsThis PET study confirmed that daily treatment of at least 1 mg sembragiline resulted in near-maximal inhibition of brain MAO-B enzyme in patients with AD.

KeywordsMonoamine oxidase inhibitor MAO-B Sembragiline Alzheimer’s disease Positron emission tomography Stefan Sturm and Anton Forsberg contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1007-s00259-016-3510-6 contains supplementary material, which is available to authorized users.

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Author: Stefan Sturm - Anton Forsberg - Stephane Nave - Per Stenkrona - Nicholas Seneca - Andrea Varrone - Robert A. Comley - Patr

Source: https://link.springer.com/







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