Thursday, July 3, 2025 7/3/2025

Development and validation of a high throughput screening assay for identification of tau aggregation inhibitors in Alzheimer's disease

Award Number: R61NS136666
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2025

Group Awards By:

View Award Description

Development and validation of a high throughput screening assay for identification of tau aggregation inhibitors in Alzheimer's disease - Abstract Alzheimer's disease (AD) is the most common type of dementia affecting a large percentage of the elderly population. A hallmark event in AD is the brain accumulation of misfolded protein aggregates in the form of amyloid and tau pathology. Amyloid pathology comprises the predominantly extracellular accumulation of amyloid-β peptide (Aβ) in diverse type of amyloid deposits. Tau pathology appears as hyperphosphorylated Tau aggregates in the form of neurofibrillary tangles (NFT) in neuronal somata and neuropil threads in neuronal dendrites. Considerable evidence indicates that the accumulation of Aβ aggregates is the initiator of AD pathogenesis, but that Tau pathology is the main executor of neurodegeneration. Despite the substantial advances in understanding the genetic, cellular and molecular pathways implicated in AD, the disease is still incurable and have few (mostly symptomatic) options for treatment. In this project we propose the discovery and development of drugs for AD treatment by focusing on inhibiting the spreading of Tau aggregates. We plan to develop a highly relevant and robust screening assay to identify Tau inhibitors based on the protein misfolding cyclic amplification (PMCA) technology invented in our lab. PMCA reproduces the seeding/nucleation process that features the formation of all misfolded protein aggregates in the brain. We have recently developed a PMCA-based assay to study the seeded polymerization of Tau aggregates. Our goal is to adapt Tau-PMCA as a high-throughput primary screening test to identify drug candidates able to inhibit misfolding and aggregation of Tau. In the R61 phase we propose to develop a high- throughput version of Tau-PMCA (HT-Tau-PMCA) assay and validate it in terms of robustness, reproducibility and specificity using standard practices in the pharmaceutical industry. We will also perform a pilot screening of 2000 compounds to evaluate assay quality and estimate the rate of hit identification. In the R33 phase we propose to perform a large screening of a chemical library containing 100,000 compounds from diverse chemical classes. Hits identified by HT-Tau-PMCA will be characterized to obtain IC50 and to analyze specificity against other misfolded proteins. Hits with IC50 < 1 µM will be characterized by their drug-like properties using in silico approaches. The best hits will be used for studies using cellular and animal models of Tau propagation. This project has the potential to identify new chemical compounds with ability to inhibit Tau seeding and spreading that can be developed as a much needed therapy for AD.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $194,226 )
2025	2025	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/27/2025	NON-COMPETING CONTINUATION	$194,226
														Subtotal = $194,226

Issue Date FY: 2024 ( Subtotal = $371,919 )
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/21/2024	NEW	$371,919
														Subtotal = $371,919

Grand Total All Awards = $566,145

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Development and validation of a high throughput screening assay for identification of tau aggregation inhibitors in Alzheimer's disease

Award Number: R61NS136666

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer