The purpose of the study is to evaluate the safety and tolerability of multiple doses of NPT088 in patients with mild to moderate probable Alzheimer's Disease. The study will also evaluate the pharmacokinetics, immunogenicity and exploratory pharmacodynamic characteristics of multiple doses of NPT088.

开始日期2016-12-01

申办/合作机构

Proclara Biosciences, Inc.

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100 项与 NPT-088 相关的临床结果

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100 项与 NPT-088 相关的转化医学

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100 项与 NPT-088 相关的专利（医药）

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项与 NPT-088 相关的文献（医药）

2017-02-16·Current Alzheimer Research4区 · 医学

Conformation as the Therapeutic Target for Neurodegenerative Diseases

4区 · 医学

Review

作者: Tsubery, Haim ; Fisher, Richard ; Krishnan, Rajaraman ; Hefti, Franz ; Lulu, Michal ; Proschitsky, Ming

Therapeutic strategies that target pathways of protein misfolding and the toxicity of intermediates along these pathways are mainly at discovery and early development stages, with the exception of monoclonal antibodies that have mainly failed to produce convincing clinical benefits in late stage trials. The clinical failures represent potentially critical lessons for future neurodegenerative disease drug development. More effective drugs may be achieved by pursuing the following two strategies. First, conformational targeting of aggregates of misfolded proteins, rather than less specific binding that includes monomer subunits, which vastly outnumber the toxic targets. Second, since neurodegenerative diseases frequently include more than one potential protein pathology, generic targeting of aggregates by shape might also be a crucial feature of a drug candidate. Incorporating both of these critical features into a viable drug candidate along with high affinity binding has not been achieved with small molecule approaches or with antibody fragments. Monoclonal antibodies developed so far are not broadly acting through conformational recognition. Using GAIM (General Amyloid Interaction Motif) represents a novel approach that incorporates high affinity conformational recognition for multiple protein assemblies, as well as recognition of an array of assemblies along the misfolding pathway between oligomers and fibers. A GAIM-Ig fusion, NPT088, is nearing clinical testing.

2016-09-01·Alzheimer's & Dementia: Translational Research & Clinical Interventions

NPT088 reduces both amyloid‐β and tau pathologies in transgenic mice

Article

作者: Mufson, Elliott J. ; Nadeem, Muhammad ; Asp, Eva ; Gannon, Kimberley S. ; Fisher, Richard ; Wright, Jason ; Solomon, Beka ; Chung, Charlotte H.‐Y. ; Proschitsky, Ming ; Gilead, Sharon ; Cullen, Valerie ; Shoaga, Shadiyat ; Levenson, Jonathan M. ; Tsubery, Haim ; Schroeter, Sally ; Carroll, Jenna C. ; Krishnan, Rajaraman ; Dodiya, Hemraj B.

AbstractIntroductionAlzheimer'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.MethodsAged 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.ResultsNPT088‐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.DiscussionThese observations establish NPT088 as a novel therapeutic approach and potential drug class that targets both Aβ and tau, the hallmark pathologies of AD.

The Journal of Prevention of Alzheimer's Disease4区 · 医学

RANDOMIZED, PLACEBO CONTROLLED TRIAL OF NPT088, A PHAGE-DERIVED, AMYLOID-TARGETED TREATMENT FOR ALZHEIMER’S DISEASE

4区 · 医学

Article

作者: J. M. Levenson ; D. Michelson ; Richard Fisher ; P. Aisen ; K. Marek ; M. Grundman ; M. Gray ; F. Hefti ; K. Magnuson

The engineered fusion protein NPT088 targets amyloid in vitro and in animal models of Alzheimer’s disease. Previous studies showed that NPT088 treatment reduced β-amyloid plaque and tau aggregate loads in mouse disease models. Here, we present the results from an initial clinical study of NPT088 in patients with mild to moderate Alzheimer’s disease. Patients were treated with 4 dose levels of NPT088 for 6 months to evaluate its safety and tolerability. Exploratory measurements included measurement of change in β-amyloid plaque and tau burden utilizing Positron Emission Tomography imaging as well as measures of Alzheimer’s disease symptoms. At endpoint NPT088 was generally safe and well-tolerated with the most prominent finding being infusion reactions in a minority of patients. No effect of NPT088 on brain plaques, tau aggregates or Alzheimer’s disease symptoms was observed.

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