# Imaging Ligands for Alpha-Synuclein Fibril Accumulation in Multiple System Atrophy

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2022 · $196,875

## Abstract

Abstract
Multiple System Atrophy (MSA) is a neurodegenerative disorder defined by the accumulation of alpha-
synuclein (Asyn) fibrils in glial cytoplasmic inclusions (GCIs). The accumulation of Asyn fibrils is a feature
shared with Parkinson disease, where Asyn fibrils accumulate in neuronal cytoplasmic and neuritic inclusions
known as Lewy bodies and Lewy neurites. Evidence from genetic, autopsy and disease mechanism studies
support Asyn fibrils as a therapeutic target. It is also a target for biomarker development. A leading priority is to
develop a PET imaging agent that can quantify the deposition of Asyn in living individuals, as a biomarker for
target engagement in clinical studies. An Asyn PET imaging agent would also improve the accuracy of
diagnosis for MSA, and provide a biomarker for disease progression. In this application we propose to screen
and identify novel leads for developing an Asyn imaging agent for MSA. We developed a new screening
approach to identify novel compounds that can be pursued as leads for the development of an Asyn imaging
agent. This new approach uses fluorescence measurements to screen natively fluorescent compounds for
binding Asyn fibrils in vitro followed by assessment of whether compounds bind to Asyn-containing GCIs in
postmortem MSA brain tissue sections. A final step is to determine whether compounds selectively bind to
GCIs but do not bind to other types of pathologic fibril accumulation in postmortem brain tissue sections.
Compounds found to have the desired properties will be radiolabeled with tritium in order to further
characterize their binding properties using radioligand binding assays and autoradiography. The compounds
identified in the project can be used as leads in further studies to develop an Asyn imaging agent. Results from
the project will also enable further optimization of this new screening approach to identify compounds with the
binding properties needed for an imaging agent.

## Key facts

- **NIH application ID:** 10452228
- **Project number:** 1R21NS123860-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** PAUL T KOTZBAUER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $196,875
- **Award type:** 1
- **Project period:** 2022-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452228

## Citation

> US National Institutes of Health, RePORTER application 10452228, Imaging Ligands for Alpha-Synuclein Fibril Accumulation in Multiple System Atrophy (1R21NS123860-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10452228. Licensed CC0.

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