NPT088 reduces both amyloid-β and tau pathologies in transgenic mice.

Abstract

INTRODUCTION:

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-IgG1-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.

• Authors: Jonathan M Levenson, Sally Schroeter, Jenna C Carroll, Valerie Cullen, Eva Asp, Ming Proschitsky, Charlotte H-Y Chung, Sharon Gilead, Muhammad Nadeem, Hemraj B Dodiya, Shadiyat Shoaga, Elliott J Mufson, Haim Tsubery, Rajaraman Krishnan, Jason Wright, Beka Solomon, Richard Fisher, Kimberley S Gannon
• Journal: Alzheimer's & dementia (New York, N. Y.) (Alzheimers Dement (N Y)) Vol. 2 Issue 3 Pg. 141-155 (Sep 2016) ISSN: 2352-8737 [Print] United States
• PMID: 29067301 (Publication Type: Journal Article)