Open AccessNPT088 reduces both amyloid‐β and tau pathologies in transgenic mice
Author(s) -
Levenson Jonathan M.,
Schroeter Sally,
Carroll Jenna C.,
Cullen Valerie,
Asp Eva,
Proschitsky Ming,
Chung Charlotte H.Y.,
Gilead Sharon,
Nadeem Muhammad,
Dodiya Hemraj B.,
Shoaga Shadiyat,
Mufson Elliott J.,
Tsubery Haim,
Krishnan Rajaraman,
Wright Jason,
Solomon Beka,
Fisher Richard,
Gan Kimberley S.
Publication year - 2016
Publication title -
alzheimer's and dementia: translational research and clinical interventions
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.49
H-Index - 30
ISSN - 2352-8737
DOI - 10.1016/j.trci.2016.06.004
Subject(s) - genetically modified mouse , senile plaques , tau pathology , amyloid (mycology) , transgene , tauopathy , neuroscience , pathology , chemistry , tau protein , atrophy , extracellular , alzheimer's disease , neurodegeneration , medicine , microbiology and biotechnology , biology , disease , biochemistry , gene
Alzheimer's disease (AD) is characterized by appearance of both extracellular senile plaques and intracellular neurofibrillary tangles, comprised of aggregates of misfolded amyloid‐β (Aβ) and hyper‐phosphorylated tau, respectively. In a previous study, we demonstrated that g3p, a capsid protein from bacteriophage M13, binds to and remodels misfolded aggregates of proteins that assume an amyloid conformation. We engineered a fusion protein (“NPT088”) consisting of the active fragment of g3p and human‐IgG 1 ‐Fc. Methods Aged Tg2576 mice or rTg4510 mice received NPT088 weekly via IP injection. Cognitive and/or functional motor endpoints were monitored during dosing. Pathology was quantified biochemically and immunohistochemically. Results NPT088‐lowered Aβ plaque and improved cognitive performance of aged Tg2576 mice. Moreover, NPT088 reduced phospho‐tau pathology, reduced brain atrophy, and improved cognition in rTg4510 mice. Discussion These observations establish NPT088 as a novel therapeutic approach and potential drug class that targets both Aβ and tau, the hallmark pathologies of AD.