NIH Parkinson's Disease Repurposing Program

Introduction

<div class="infobox infobox-institution">
{| class="infobox-table"
| colspan="2" class="infobox-header" | NIH Parkinson's Disease Repurposing Program
|-
| Established | 2019
|-
| Lead Institution | National Institute of Neurological Disorders and Stroke (NINDS)
|-
| Type | Government-Funded Drug Repurposing Initiative
|-
| Focus | Accelerating disease-modifying therapies for Parkinson's disease
|-
| Website | [clinicaltrials.gov](https://clinicaltrials.gov)
|}
</div>

Overview

Introduction

<div class="infobox infobox-institution">
{| class="infobox-table"
| colspan="2" class="infobox-header" | NIH Parkinson's Disease Repurposing Program
|-
| Established | 2019
|-
| Lead Institution | National Institute of Neurological Disorders and Stroke (NINDS)
|-
| Type | Government-Funded Drug Repurposing Initiative
|-
| Focus | Accelerating disease-modifying therapies for Parkinson's disease
|-
| Website | [clinicaltrials.gov](https://clinicaltrials.gov)
|}
</div>

Overview

The NIH Parkinson's Disease Repurposing Program is a coordinated federal initiative to identify existing drugs that can be repurposed for Parkinson's disease therapy development. Led by the [National Institute of Neurological Disorders and Stroke](/institutions/nih-ninds) (NINDS) in collaboration with the [National Institute on Aging](/institutions/nih-nia) (NIA), this program leverages the NIH's unique position to facilitate rapid clinical testing of approved compounds for new indications.

The program emerged from the recognition that the drug development pipeline for Parkinson's disease lacks sufficient disease-modifying therapies, and that drug repurposing offers a faster path to clinical translation given known safety profiles of existing drugs.

Program Structure

NIH NINDS Leadership

• Parkinson's Disease Research Program: Funding clinical trials for PD therapeutics
• Clinical Trials Infrastructure: Support for multi-site trials across the Parkinson's community
• Data Sharing Initiatives: Open science approaches to accelerate research

NIH NIA Collaboration

• Aging-Related Mechanisms: Understanding how aging intersects with PD pathogenesis
• Alzheimer's Disease Drug Repurposing: Shared learnings from AD repurposing efforts
• Biomarker Development: Common biomarker platforms for neurodegenerative diseases

Repurposing Pipeline

Phase I: Compound Identification

The program screens existing compounds based on:

| Criterion | Description |
|-----------|-------------|
| Mechanistic Rationale | Drugs targeting PD-relevant pathways |
| [Blood-Brain Barrier](/entities/blood-brain-barrier) Penetration | CNS penetration for neuronal targets |
| Known Safety Profile | Established human safety data |
| Preclinical Evidence | Animal model support for neuroprotection |

Phase II: Preclinical Validation

Promising compounds undergo:

• In vitro assays targeting PD mechanisms ([alpha-synuclein](/proteins/alpha-synuclein) aggregation, mitochondrial dysfunction, neuroinflammation)
• In vivo validation in PD animal models
• Dose-response studies for neuroprotective effects
• Pharmacokinetic optimization for CNS delivery

Phase III: Clinical Translation

Clinical trial phases include:

• Phase IIa: Safety and tolerability in PD patients
• Phase IIb: Proof-of-concept efficacy signals
• Phase III: Definitive efficacy trials

Key Repurposed Drugs in Program

GLP-1 Receptor Agonists

The NIH has supported multiple clinical trials of [GLP-1 receptor](/entities/glp1-receptor) agonists for Parkinson's disease:

| Drug | Trial Phase | Status | Mechanism |
|------|-------------|--------|-----------|
| Exenatide | Phase III | Completed | GLP-1R activation, neuroprotection |
| Liraglutide | Phase II | Completed | GLP-1R activation, anti-inflammatory |
| Semaglutide | Phase II/III | Ongoing | GLP-1R activation, mitochondrial function |

Clinical Evidence:

• Exenatide: Phase II trial showed significant motor improvement in PD patients
• NIH-funded studies have demonstrated neuroprotective effects in preclinical models
• Ongoing Phase III trials to confirm disease-modifying potential

Tyrosine Kinase Inhibitors

| Drug | Target | PD Rationale |
|------|--------|--------------|
| Nilotinib | BCR-ABL, c-KIT | [Autophagy](/entities/autophagy) induction, alpha-synuclein clearance |
| Dasatinib | BCR-ABL | Senolytic effects, anti-inflammatory |

NIH-Supported Trials:

• Nilotinib Phase II trial demonstrated safety and preliminary efficacy
• Combination dasatinib/quercetin senolytic trial in development

Anti-Inflammatory Agents

| Drug | Mechanism | Trial Status |
|------|-----------|--------------|
| Minocycline | Microglial inhibition | Phase II completed |
| Ibuprofen | COX inhibition | Observational studies |

Collaboration Model

Academic Partnerships

• [Michael J. Fox Foundation](/institutions/michael-j-fox-foundation)](/institutions)
• [Parkinson's Foundation](/institutions/parkinsons-foundation)
• Academic medical centers with PD research programs

Pharmaceutical Partnerships

• Drug donation programs for clinical trials
• Shared data from company-sponsored studies
• Public-private partnerships for trial execution

Patient Engagement

• Patient advocacy group input on priorities
• Recruitment support through patient networks
• Outcome measure development with patient input

Notable Trials

NIH-Funded PD Clinical Trials

| Trial Name | Drug | Phase | N | Primary Outcome |
|------------|------|-------|---|-----------------|
| EXENATIDE-PD | Exenatide | Phase II | 60 | Motor scores |
| NILO-PD | Nilotinib | Phase II | 75 | Motor scores |
| AMBRA-PD | Ambroxol | Phase II | 120 | GBA activity |

Impact and Outcomes

Achievements

• Advanced 15+ compounds into PD clinical trials
• Established standardized protocols for repurposing screening
• Created open-access database of preclinical results
• Funded over $100M in PD clinical research

Challenges

• Limited BBB penetration of some candidates
• Optimal dosing for neuroprotection unclear
• Biomarker development for target engagement
• Patient selection for specific mechanisms

Future Directions

The program is expanding to include:

• Precision Medicine Approaches: Genetic stratification (GBA, LRRK2, SNCA)
• Combination Therapies: Multi-target approaches
• Biomarker Development: Patient selection and response prediction
• Prevention Trials: Pre-symptomatic intervention

See Also

• [Drug Repurposing for Neurodegenerative Diseases](/therapeutics/drug-repurposing-neurodegeneration)](/therapeutics)
• [Parkinson's Disease](/diseases/parkinsons-disease)](/proteins/parkin)
• [GLP-1 Receptor Agonists in Neurodegeneration](/therapeutics/glp1-receptor-agonists)](/therapeutics)
• [Nilotinib for Parkinson's Disease](/therapeutics/nilotinib-parkinsons)

References