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O2‐13‐04: Early Clinical Results and Preclinical Validation of the O‐Glcnacase (OGA) Inhibitor Mk‐8719 as a Novel Therapeutic for the Treatment of Tauopathies
Author(s) -
Smith Sean M.,
Struyk Arie,
Jonathan Daniel,
Declercq Ruben,
Marcus Jacob,
Toolan Dawn,
Wang Xiaohai,
Schachter Joel B.,
Cosden Mali,
Pearson Michelle,
Hess Fred,
Selnick Harold,
Salinas Cristian,
Li Wenping,
Duffy Joseph,
McEachern Ernest,
Vocadlo David,
Renger John J.,
Eric Hostetler D.,
Forman Mark,
Schoepp Darryle
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.469
Subject(s) - progressive supranuclear palsy , tolerability , tauopathy , medicine , genetically modified mouse , pharmacology , transgene , atrophy , chemistry , biochemistry , neurodegeneration , disease , adverse effect , gene
cant decrease of human Tau multimers (HT7/HT7 setup), as well as a significant decrease of a misfolded Tau (MC-1/HT7 setup) in a total brain fraction.A trend to decrease humanTau phosphorylated at pS396 in different brain fractions was also observed. ACI-35 treatment significantly improved the rotarod performance in both the transgenic hTauP301S-Tg model and the AAV-TauP301S spreading model. Conclusions: The study demonstrated that active immunization with ACI-35 significantly decreased human pathological Tau species in different brain fractions and ameliorated the clinical phenotype in two different mouse models of tauopathy.