# Evaluating cell type-specific non-dopaminergics as a Parkinson's treatment paradigm

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $338,218

## Abstract

Parkinson’s disease (PD) is a debilitating neurodegenerative movement disorder, characterized by loss of
dopaminergic cells. Primary treatments have relied on replenishing dopamine (e.g. levodopa), however, over
time these drugs lose efficacy and lead to incapacitating levodopa induced dyskinesias (LID). These
shortcomings suggest that PD cannot be understood or treated by dopaminergic pathways alone. Among non-
dopaminergic mechanisms, synaptic receptors are prime candidates for manipulation, however relevant
experiments have thus far not yielded promising results. These interventions have suffered from a lack of cellular
specificity—the striatum, robustly implicated in PD, contains distinct cell types with opposing behavioral
functionality. The inability to target pharmacological agents to just one of these cell types has produced a major
gap in the understanding and treatment of PD. To address this limitation, we recently developed DART (Drugs
Acutely Restricted by Tethering), a genetically encoded drug-targeting technology that offers the first opportunity
to establish behavioral roles of a specific receptor on a defined cell type. In this proposal we will apply cell type-
specific synaptic receptor interventions in PD and LID in mouse models. This work will provide unprecedented
circuit and molecular insights into PD and LID pathophysiology. In addition, it may provide a roadmap for
cell type-specific restriction as a potentially general paradigm for increasing drug efficacy.

## Key facts

- **NIH application ID:** 10445236
- **Project number:** 5R01NS107472-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Michael R Tadross
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $338,218
- **Award type:** 5
- **Project period:** 2018-09-30 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445236

## Citation

> US National Institutes of Health, RePORTER application 10445236, Evaluating cell type-specific non-dopaminergics as a Parkinson's treatment paradigm (5R01NS107472-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10445236. Licensed CC0.

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