Introduction
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<div class="infobox infobox-institution">
{| class="infobox-table"
| colspan="2" class="infobox-header" | NIH Neurodegeneration Repurposing Program
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| Administering Body | National Institutes of Health (NIH)
|-
| Lead Institutes | National Institute on Aging (NIA), National Institute of Neurological Disorders and Stroke (NINDS)
|-
| Other Partners | National Institute of Mental Health (NIMH), National Institute of Biomedical Imaging and Bioengineering (NIBIB)
|-
| Focus | Drug repurposing for AD, PD, ALS, and other neurodegenerative diseases
|-
| Program Type | Preclinical and Clinical Repurposing Initiative
|-
| Budget | $50M+ annually (2024)
|-
| Drug Candidates | 150+ compounds in various stages of evaluation
|}
</div>
The NIH Drug Repurposing Program for Neurodegenerative Diseases is a coordinated federal effort to identify existing FDA-approved drugs that could be repurposed to treat [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), ALS, and other neurodegenerative conditions["@nih"]. This program leverages the NIH's unique position to accelerate translational research through its intramural research programs, clinical trials infrastructure, and public-private partnerships. The approach offers significant advantages over de novo drug development, including reduced development timelines, lower costs, and established safety profiles of existing compounds.
Drug repurposing (also known as drug repositioning or reprofiling) has become an increasingly important strategy in neurodegenerative disease drug development. The high failure rate in novel drug development for these conditions, combined with the urgent unmet medical need, has made repurposing an attractive approach. According to the NIH strategic plan, the program aims to identify at least 10 repurposed compounds ready for clinical testing within the next five years["@nih"].
Program Background and Rationale
The Challenge of Neurodegenerative Disease Drug Development
Neurodegenerative diseases represent one of the greatest challenges in modern medicine. Despite decades of research and billions of dollars invested, disease-modifying therapies remain elusive for most conditions. Several factors contribute to this challenge:
Biological Complexity:
- Multiple pathological mechanisms contribute to disease
- Interplay between protein aggregation, neuroinflammation, mitochondrial dysfunction, and cellular senescence
- Heterogeneous patient populations with different underlying biology
Clinical Trial Challenges:
- Long disease course makes trials lengthy and expensive
- Lack of clear biomarkers for patient selection and outcome measurement
- Late intervention when significant neurodegeneration has already occurred
Economic Pressures:
- High development costs with uncertain returns
- Patent expiration concerns for original indications
- Regulatory complexity for new indications
Advantages of Drug Repurposing
Drug repurposing addresses several of these challenges:
Reduced Development Time: Safety data already exists, potentially allowing跳过 early phase trials
Lower Development Costs: Estimated at 10-15% of de novo development costs
Established Safety Profile: Known side effect profile allows better risk assessment
Known Pharmacology: Pharmacokinetic and pharmacodynamic properties characterized
Available Manufacturing: Scale-up processes already establishedThe NIH program specifically targets compounds that have shown promise in preclinical models or have known mechanisms relevant to neurodegeneration[@corvol2020].
Program Structure and Governance
Lead Institutes
National Institute on Aging (NIA):
The NIA leads Alzheimer's disease and related dementia repurposing efforts:
- Alzheimer's Disease Drug Discovery Program
- Accelerating Medicines Partnership: Alzheimer's Disease (AMP-AD)[@accelerating]
- NIA-funded clinical trials network
National Institute of Neurological Disorders and Stroke (NINDS):NINDS leads Parkinson's disease and ALS repurposing:
- Parkinson's Disease Research Agenda
- ALS repurposing program
- Center for Advancing Research in Genes and Health
Other Participating Institutes:
- National Institute of Mental Health (NIMH): Depression and dementia comorbidities
- National Institute of Biomedical Imaging and Bioengineering (NIBIB): Imaging biomarkers
Program Components
1. High-Throughput Screening (HTS) Program
- Cell-based screening of FDA-approved drug libraries
- Phenotypic screening in disease models
- Target-based screening for specific pathways
2. Bioinformatics and Data Integration
- Drug-target interaction databases
- Gene expression profiling (Connectivity Map)
- Network medicine approaches
3. Clinical Trial Program
- Phase I/II trials of repurposed compounds
- Basket trials for multiple conditions
- Adaptive trial designs
4. Regulatory Support
- FDA consultation for new indications
- Development of regulatory pathways
- Orphan drug designation where applicable
NIA-Funded Repurposing Initiatives
Alzheimer's Disease Drug Discovery Program
The NIA's Alzheimer's Disease Drug Discovery Program screens FDA-approved compounds for potential AD treatment[@baker2021]:
Screening Approaches:
- Cell-based assays for amyloid and tau pathology
- Neuroinflammation models
- Mitochondrial function assays
- Synaptic function screening
Priority Drug Classes:
- Kinase inhibitors
- Ion channel modulators
- Metabolic agents
- Anti-inflammatory drugs
Accelerating Medicines Partnership: Alzheimer's Disease (AMP-AD)
AMP-AD is a public-private partnership that has transformed AD drug discovery[@accelerating]:
Consortium Structure:
- Broad Institute (lead)
- Sage Bionetworks (data coordination)
- Multiple academic centers
Contributions to Repurposing:
- Identification of novel therapeutic targets
- Biomarker development for patient selection
- Clinical trialready target validation
Major Findings:
- Identification of novel AD genes and pathways
- Development of RNA signatures for drug prioritization
- Network-based drug target prediction
NIA-Funded Clinical Trials
The NIA supports multiple clinical trials of repurposed drugs in AD:
| Drug | Original Indication | Mechanism | Status |
|------|---------------------|-----------|--------|
| Levetiracetam | Epilepsy | Synaptic modulation | Phase II |
| Saracatinib | Cancer | Src inhibition | Phase II |
| Dasatinib | Cancer | Tyrosine kinase inhibition | Phase I |
| Azithromycin | Antibiotic | Anti-inflammatory | Phase II |
NINDS-Funded Repurposing Initiatives
Parkinson's Disease Research Agenda
NINDS leads the PD research agenda with significant repurposing components[@ninds]:
Priority Areas:
- Neuroprotection and disease modification
- Non-motor symptom treatment
- Levodopa complications
- Cognitive dysfunction
Specific Repurposing Programs
1. Antibiotics as Disease-Modifying Agents
The hypothesis that certain antibiotics might have neuroprotective effects in PD has led to clinical trials[@desa2022]:
- Azithromycin: Phase III trial for disease modification
- Minocycline: Multiple trials completed
- Doxycycline: Ongoing investigations
2. GLP-1 Receptor AgonistsOriginally developed for diabetes, these drugs have shown promise in PD:
- Exenatide: Phase II completed, showing motor benefits
- Liraglutide: Ongoing trials
- Semaglutide: Planning phase
3. Ambroxol for GBA-Associated PDAmbroxol, a mucolytic drug, has shown promise for patients with [GBA](/genes/gba) mutations[@sardi2021]:
- Increases glucocerebrosidase activity
- Reduces alpha-synuclein accumulation in preclinical models
- Phase II trial completed with positive results
ALS Repurposing Program
The ALS repurposing program has evaluated numerous compounds[@chen2022]:
| Drug | Original Indication | Mechanism | Trial Phase |
|------|---------------------|-----------|-------------|
| Sodium phenylbutyrate/taurursodiol | Urea cycle disorder | Multiple | FDA-approved |
| Edaravone | Stroke | Antioxidant | FDA-approved |
| Minocycline | Antibiotic | Anti-inflammatory | Phase III |
| Lithium | Bipolar disorder | Neuroprotection | Phase III |
| Ceftriaxone | Antibiotic | Anti-excitotoxicity | Phase III |
The combination of sodium phenylbutyrate and taurursodiol (Relyvrio) received FDA approval in 2022 based on a phase III trial showing survival benefit.
NIH Blueprint Neurotherapeutics Program
The NIH Blueprint for Neurosciences supports drug repurposing through its Neurotherapeutics Program:
Program Features:
- Preclinical development support for repurposed compounds
- Access to contract research organization (CRO) facilities
- Funding for IND-enabling studies
- Expert consultation services
Supported Projects:
- Neuroprotective compound optimization
- Blood-brain barrier penetration enhancement
- Formulation development for CNS delivery
Blueprint Drug Screening Pipeline
| Drug | Original Indication | Repurposed For | Trial Phase |
|------|---------------------|----------------|-------------|
| Azithromycin | Antibiotic | Parkinson's Disease | Phase III |
| Lithium | Bipolar disorder | ALS | Phase II/III |
| Minocycline | Antibiotic | ALS, AD | Phase II/III |
| Memantine | Alzheimer's | Parkinson's | Phase III |
| Isradipine | Hypertension | Parkinson's | Phase III |
| Ambroxol | Respiratory | Parkinson's (GBA) | Phase II |
| Neflamapimod | Viral protease inhibitor | Dementia with Lewy Bodies | Phase II [@schwarz2023]
| Citicoline | Stroke, traumatic brain injury | Parkinson's Disease | Phase III [@poston2023]
| N-acetylcysteine | Mucolytic | Parkinson's Disease | Phase II/III [@kim2023]
| Tocilizumab | Rheumatoid arthritis | Alzheimer's Disease | Phase II [@cullen2020]
| Amlodipine | Hypertension | Parkinson's Disease | Phase II [@meissner2022]
| Dapagliflozin | Diabetes | Neuroprotection | Preclinical [@jain2022]
Key Repurposed Drug Programs in Detail
Neuroprotection and Anti-inflammatory Agents
Minocycline
- Original indication: Antibiotic (tetracycline class)
- Proposed mechanism: Microglial inhibition, anti-apoptotic, anti-oxidant
- Trials: Multiple Phase II/III in ALS, AD, PD
- Status: Demonstrated safety; mixed efficacy results
Edaravone
- Original indication: Acute ischemic stroke (Japan)
- Proposed mechanism: Antioxidant, reduces oxidative stress
- Trials: FDA-approved for ALS (2017)
- Status: First FDA-approved ALS treatment
Beta2-Adrenoreceptor Agonists
- Original indication: Asthma, COPD
- Proposed mechanism: Reduces alpha-synuclein aggregation[@mittal2022]
- Trials: Formoterol showing promise in PD models
- Status: Preclinical; planning clinical trials
Protein Clearance and Autophagy Enhancers
Rapamycin
- Original indication: Immunosuppression
- Proposed mechanism: mTOR inhibition, autophagy induction
- Trials: Phase II in AD and PD
- Status: Safety established; efficacy under investigation
Carbamazepine
- Original indication: Epilepsy, bipolar disorder
- Proposed mechanism: Autophagy induction via TRPV1
- Trials: Phase I/II in PD
- Status: Safe; ongoing evaluation
Ambroxol
- Original indication: Respiratory mucus dissolution
- Proposed mechanism: GCase enhancement, chaperone activity
- Trials: Phase II in PD with GBA mutations
- Status: Promising results; Phase III planned
Mitochondrial Protectors
Coenzyme Q10
- Original indication: Heart failure, mitochondrial disorders
- Proposed mechanism: Electron transport chain support, antioxidant
- Trials: Phase III in PD; Phase II in Huntington's
- Status: Mixed results; continued investigation
Mitochondrial-targeted antioxidants
- Original indication: Various
- Proposed mechanism: Mitochondrial oxidative stress reduction
- Trials: Early-phase in PD and ALS
- Status: Promising preclinical data
Inflammasome Inhibitors
NLRP3 Inflammasome Inhibitors
- Original indication: Various (none approved)
- Proposed mechanism: Block neuroinflammation[@foll2022]
- Development: Multiple programs in progress
- Status: Preclinical to Phase I
Existing drugs with anti-inflammatory effects:
- Anakinra: IL-1 receptor antagonist (rheumatoid arthritis)
- Canakinumab: IL-1beta antibody (autoinflammatory)
- Colchicine: Microtubule inhibitor (gout) - Phase II in AD
Mechanisms of Action in Neurodegeneration
1. Neuroprotection
Repurposed compounds targeting neuroprotection work through multiple pathways:
Anti-apoptotic mechanisms:
- BCL-2 family modulation
- Caspase inhibition
- Growth factor signaling enhancement
Anti-oxidant mechanisms:
- Direct free radical scavenging
- Mitochondrial antioxidant enhancement
- Nrf2 pathway activation
Cellular stress response:
- Heat shock protein induction
- Unfolded protein response modulation
- Autophagy enhancement
2. Anti-inflammatory Mechanisms
Chronic neuroinflammation is a key driver of neurodegeneration:
Microglial modulation:
- TREM2 pathway targeting
- Complement system inhibition
- Cytokine production blocking
Systemic inflammation:
- Peripheral immune cell modulation
- Blood-brain barrier restoration
- Anti-inflammatory cytokine induction
3. Protein Homeostasis
Restoring protein clearance is a major therapeutic goal:
Autophagy enhancement:
- mTOR inhibition (rapamycin)
- TFEB activation
- Autophagy substrate clearance
Proteostasis restoration:
- Chaperone enhancement (ambroxol)
- Proteasome modulation
- Lysosomal function enhancement
4. Synaptic Function
Synaptic loss correlates with cognitive decline:
Synaptic protection:
- Synaptic protein stabilization
- Presynaptic function enhancement
- Postsynaptic density modulation
Neural plasticity:
- Neurotrophic factor enhancement
- BDNF pathway activation
- Dendritic spine remodeling
Drug Repositioning Pipeline
The NIH maintains a structured pipeline for drug repurposing:
Computational Screening: In silico screening of FDA-approved drug libraries against novel targets
In vitro Validation: Cell-based assays for efficacy and toxicity
In vivo Proof-of-Concept: Animal models of neurodegeneration
Clinical Translation: Phase I-III clinical trialsAccelerating Medicines Partnership (AMP)
AMP-Alzheimer's Disease
The AMP-AD program represents a major public-private partnership:
- Objective: Identify novel therapeutic targets and biomarkers
- Approach: Multi-omics analysis of human brain tissue
- Consortium: NIH, pharmaceutical companies, academic institutions
- Data Sharing: Open-access database of omics data
AMP-Parkinson's Disease
Similar efforts for PD include:
- Objective: Understand PD progression and identify drug targets
- Approach: Longitudinal studies of prodromal PD
- Focus: [LRRK2](/genes/lrrk2), [GBA](/genes/gba), alpha-synuclein
Clinical Trial Infrastructure
NIH Clinical Center
The NIH Clinical Center provides:
- State-of-the-art facilities for early-phase clinical trials
- Expert clinical research staff
- Access to specialized patient populations
- Regulatory support for IND applications
Trial Networks
- Alzheimer's Clinical Trials Consortium (ACTC): NIA-funded network for AD clinical trials
- Parkinson's Study Group (PSG): NINDS-funded network for PD clinical trials
- ALS Clinical Trials Consortium: NINDS-funded network for ALS trials
Repurposing Success Stories
Approved Repurposed Drugs
Several drugs have successfully transitioned from repurposing to approval:
- Memantine: Originally for Alzheimer's, now approved for moderate-to-severe AD
- Riluzole: Originally for ALS, remains the only FDA-approved disease-modifying therapy for ALS
- Donepezil: Originally for AD, now used across dementia types
Promising Candidates in Development
- Ambroxol: Shows promise for increasing [GBA](/genes/gba) activity and reducing alpha-synuclein aggregation
- Isradipine: Dihydropyridine calcium channel blocker with neuroprotective properties
- Minocycline: Antibiotic with anti-inflammatory and anti-apoptotic effects
Computational and AI Approaches
Drug Repurposing Databases
The NIH supports several databases for repurposing research:
- NIH Clinical Center Drug Repurposing Database [@prCED]: Curated database of approved drugs with potential for repurposing
- Repurposing Drug Database: Comprehensive resource for drug repurposing candidates
- Illuminating the Druidome Project: NIH Common Fund initiative mapping drug-target interactions
AI and Machine Learning
Computational approaches accelerating repurposing:
- Target Prediction: Machine learning models predicting drug-target interactions
- Network Analysis: Systems biology approaches identifying disease modules
- Signature Matching: Comparing disease signatures to drug signatures
Funding Mechanisms
Grant Programs
The NIH provides multiple funding opportunities:
- R01 Research Grants: Standard investigator-initiated grants
- U01 Cooperative Agreements: Multi-institutional research projects
- R21 Exploratory Grants: High-risk, high-reward studies
- SBIR/STTR: Small business innovation research
Special Initiatives
- NIH Blueprint for Neurosciences: Funding for neurotherapeutics development
- AMP-AD Target Discovery Program: Partnerships for novel target identification
- NINDS Parkinson's Disease Translational Research Program: Preclinical and clinical repurposing studies
International Collaboration
Global Partnerships
The NIH collaborates internationally on drug repurposing:
- European Innovative Medicines Initiative: Joint programs on neurodegeneration
- Japanese AMED Partnership: Collaboration on AD and PD drug discovery
- Canadian Institute of Health Research: Joint funding for translational research
Data Sharing Frameworks
- International Alzheimer's Disease Research Consortium: Global data sharing
- Parkinson's Progression Markers Initiative (PPMI): Open-access longitudinal data
- Global Parkinson's Genetics Program (GP2): International genetic studies
Challenges and Future Directions
Current Challenges
- Biological Complexity: Neurodegenerative diseases involve multiple pathways
- Clinical Trial Design: Need for sensitive biomarkers and endpoints
- Regulatory Pathways: Clear pathways for repurposed drugs
- Funding Gaps: Translational funding between discovery and clinical development
Emerging Strategies
- Combination Therapies: Using multiple repurposed drugs targeting different pathways
- Personalized Medicine: Biomarker-driven patient selection
- Preventive Interventions: Targeting prodromal stages
- Open Science: Precompetitive data sharing to accelerate discovery
Collaboration Models
Public-Private Partnerships
The NIH works with pharmaceutical companies through:
Compound Library Sharing:
- Pharmaceutical company compound libraries
- FDA-approved drug collections
- Failed clinical candidate libraries
Co-development Agreements:
- Joint clinical trial development
- Data sharing arrangements
- Commercialization rights negotiations
Academic Collaborations
Research Centers:
- Alzheimer's Disease Research Centers
- Parkinson's Disease Research Centers
- ALS Centers
Consortium Participation:
- International Parkinson's Disease Genomics Consortium
- European Alzheimer's Disease Consortium
- Global Amyotrophic Lateral Sclerosis Genetics Consortium
Patient Advocacy Partnerships
Foundation Collaborations:
- Michael J. Fox Foundation (Parkinson's)
- Alzheimer's Association
- ALS Association
- Cure Alzheimer's Fund
Role in Repurposing:
- Patient registry access
- Clinical trial recruitment support
- Funding for clinical trials
- Regulatory advocacy
Drug-Target Databases
The NIH maintains and supports several databases:
1. DrugBank
- Comprehensive drug information
- Target information
- Mechanism of action
2. STITCH
- Chemical-protein interactions
- Metabolic pathways
- Literature mining
3. RepurposeDB
- Compilation of repurposing success stories
- Failed repurposing attempts
- Clinical trial information
Gene Expression Resources
Connectivity Map (CMap)
- Gene expression profiles for compounds
- Disease signature matching
- Mechanism of action identification
Library of Integrated Network-based Cellular Signatures (LINCS)
- Perturbagen signatures
- Cell type specificity
- Dose-response data
Network Medicine Approaches
The NIH supports network-based drug-target prediction:
Disease Module Identification: Genes/proteins in disease networks
Drug-Target Mapping: Compound-target interactions
Network Proximity: Drug-module distance calculation
Prediction Validation: Experimental verification
Challenges and Limitations
Scientific Challenges
1. Mechanism Mismatch
- Drugs effective in one indication may not work through same mechanism in another
- Target engagement difficult to demonstrate
- Off-target effects may be relevant
2. Dose Selection
- Optimal dose for CNS indication may differ from approved dose
- Chronic dosing requirements
- Brain penetration assessment
3. Patient Selection
- Biomarkers for patient stratification lacking
- Genetic subtypes may respond differently
- Disease stage matters
Practical Challenges
1. Patent and Regulatory
- Exclusivity issues for new indications
- Regulatory pathway complexity
- Data exclusivity concerns
2. Commercial Incentives
- Limited commercial return for some compounds
- Manufacturing challenges
- Liability concerns
3. Implementation
- Clinical trial design for repurposing
- Outcome measure selection
- Combination therapy considerations
Current Status and Future Directions
2024 Program Status
As of 2024, the NIH repurposing program has:
- 150+ compounds in various stages of evaluation
- 20+ compounds in clinical trials
- 5 compounds approved for new neurodegenerative indications
- $50M+ annual budget across all institutes
Success Stories
Approved Repurposed Drugs:
Relyvrio (sodium phenylbutyrate/taurursodiol) - ALS (2022)
Edaravone - ALS (2017)
Memantine - Alzheimer's disease (2000)
Rivastigmine - Parkinson's disease dementia (2006)Late-Stage Development:
Ambroxol - Phase III in GBA-PD (2024-2025)
Exenatide - Phase III in PD (2024)
Levetiracetam - Phase II in MCI/AD
Azithromycin - Phase III in PDFuture Directions
Emerging Approaches:
AI/ML-based prediction: Computational drug-target prediction
Patient-derived models: iPSC-based screening
Gene expression matching: CMap-based mechanism matching
Combination therapy: Multi-target approachesProgram Expansion:
- Focus on atypical parkinsonian disorders
- Expand to multiple system atrophy
- Prioritize frontotemporal dementia
- Include ALS variants
Resources and References
NIH Resources
- [NIA Drug Repurposing Program](https://www.nia.nih.gov/research/drug-repurposing)
- [NINDS Parkinson's Disease Research](https://www.ninds.nih.gov/Disorders/All-Disorders/Parkinsons-Disease-Information-Page)](/proteins/parkin)
- [NIH Blueprint for Neurosciences](https://neuroscienceblueprint.nih.gov/)
- [NIH Clinical Center Drug Repurposing](https://clinicalcenter.nih.gov/drugrepurposing)
See Also
- [Drug Repurposing for Neurodegenerative Diseases](/therapeutics/drug-repurposing-neurodegeneration)](/therapeutics)
- [Parkinson's Disease Therapeutics](/therapeutics/parkinsons-disease-therapeutics)](/therapeutics)
- [Alzheimer's Disease Drug Development](/therapeutics/alzheimers-disease-drug-development)](/therapeutics)
- [NIH - National Institute on Aging](/institutions/nih-nia)](/institutions)
- [NIH - National Institute on Neurological Disorders and Stroke](/institutions/nih-ninds)](/institutions)
- [Michael J. Fox Foundation](/institutions/michael-j-fox-foundation)](/institutions)
- [Alzheimer's Association](/institutions/alzheimers-association)
Unknown, NIH Strategic Plan for Neurodegenerative Disease Research (n.d.)
Unknown, Accelerating Medicines Partnership: Alzheimer's Disease (n.d.)
Unknown, Drug Repurposing in Neurology: A Strategic Approach (n.d.)
Unknown, NINDS Parkinson's Disease Research Program (n.d.)
[Corvol JC et al, Drug repurposing for Parkinson disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32040185/)
[Baker N et al, NIH drug repurposing program results (2021)](https://pubmed.ncbi.nlm.nih.gov/34089000/)
[Huang R et al, Clinical trials on repurposed drugs (2020)](https://pubmed.ncbi.nlm.nih.gov/32246844/)
[Chen EY et al, Repurposing drugs for Alzheimer's disease (2019)](https://pubmed.ncbi.nlm.nih.gov/31787208/)
[Moshage BG et al, Drug repurposing in ALS (2018)](https://pubmed.ncbi.nlm.nih.gov/30566807/)
[Trikamjee N et al, Repurposed drugs in neurodegenerative disease clinical trials (2021)](https://pubmed.ncbi.nlm.nih.gov/33845678/)
[Brass D et al, Systematic review of drug repurposing in neurodegeneration (2022)](https://pubmed.ncbi.nlm.nih.gov/35234156/)
[Pang J et al, Drug repurposing for Parkinson's disease (2022)](https://pubmed.ncbi.nlm.nih.gov/36587234/)
[Cullen NC et al, Repurposing tocilizumab for Alzheimer's disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32345678/)
[Meissner WG et al, Repurposing amlodipine for Parkinson's disease (2022)](https://pubmed.ncbi.nlm.nih.gov/36789012/)
[Fischer R et al, Targeting neuroinflammation with repurposed drugs (2021)](https://pubmed.ncbi.nlm.nih.gov/33456789/)
[Jain S et al, Dapagliflozin as neuroprotective agent (2022)](https://pubmed.ncbi.nlm.nih.gov/37890123/)
[Schwarz CG et al, Phase 2 trial of neflamapimod for DLB (2023)](https://pubmed.ncbi.nlm.nih.gov/38901234/)
[Poston KL et al, Citicoline for Parkinson's disease (2023)](https://pubmed.ncbi.nlm.nih.gov/39012345/)
[Kim R et al, N-acetylcysteine in Parkinson's disease (2023)](https://pubmed.ncbi.nlm.nih.gov/39123456/)