# Immunotherapy Targeting Tau Aggregate Polymorphs

> **NIH NIH RF1** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2022 · $2,009,600

## Abstract

Project Summary
Pathological aggregation of the microtubule-associated protein tau and its subsequent accumulation into
neurofibrillary tangles (NFTs) or other hyperphosphorylated tau-containing inclusions are defining
histopathological features of frontotemporal lobar degeneration (FTLD) and many other neurodegenerative
conditions, collectively known as tauopathies, including Pick’s disease (PiD), progressive supranuclear palsy
(PSP), corticobasal degeneration (CBD), Alzheimer’s disease (AD), dementia with Lewy bodies (DLB),
Parkinson’s disease (PD), and even traumatic brain injury (TBI). Recent studies suggest that the most
pathogenic tau species are soluble oligomers. We created several novel tau oligomer-specific monoclonal
antibodies (TOMA clones) that specifically recognize tau oligomers but do not recognize functional tau monomer
in vitro, these antibodies recognize non-continues epitopes in the middle and c-terminal part of tau protein. TOMA
clones are potent neutralizing mAbs that effectively and specifically remove toxic tau oligomers and have potential
therapeutic and diagnostic applications. Moreover, we recently established the specificity and efficacy of one of
our novel TOMA clones in three different mouse models.
We hypothesize that tau forms conformationally distinct toxic oligomeric strains/polymorphs. Herein we will
determine the efficacy of four TOMA clones on the propagation of disease relevant tau oligomeric
strains/polymorphs, and their efficacy to specifically targeting specific disease relevant tau strains/polymorphs
through passive immunotherapy. Moreover, we will generate humanized TOMA clones with the ultimate goal of
developing antibodies that can target aberrant tau species in clinical settings.
The successful completion of this research project will deliver very compelling data that will move the tau field
forward and facilitate the clinical development of safe, effective, personalized therapeutic strategies for
neurodegenerative tauopathies.

## Key facts

- **NIH application ID:** 10448132
- **Project number:** 1RF1AG077484-01
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Rakez Kayed
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,009,600
- **Award type:** 1
- **Project period:** 2022-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448132

## Citation

> US National Institutes of Health, RePORTER application 10448132, Immunotherapy Targeting Tau Aggregate Polymorphs (1RF1AG077484-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10448132. Licensed CC0.

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