NIH CTSA PSP Biospecimen Repository (NCT05067192)
Overview
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...NIH CTSA PSP Biospecimen Repository (NCT05067192)
Overview
Mermaid diagram (expand to render)
This study establishes a biospecimen repository for Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD), Corticobasal Syndrome (CBS), and related neurodegenerative disorders. The repository collects DNA, plasma, cerebrospinal fluid (CSF), and tissue samples to support research on disease mechanisms, biomarkers, and therapeutic development["@Boxer_2020"].
Study Details
| Parameter | Value |
|-----------|-------|
| NCT Number | NCT05067192 |
| Status | Recruiting |
| Study Type | Observational |
| Conditions | PSP, CBS, CBD, FTLD |
| Sites | Multiple US sites through NIH CTSA program |
Scientific Background
Tauopathies Overview
PSP and CBD belong to a group of neurodegenerative disorders classified as tauopathies, characterized by abnormal accumulation of the tau protein in the brain[@Williams_2021]. These disorders share common pathological features but present with distinct clinical phenotypes.
Progressive Supranuclear Palsy (PSP)
PSP is a 4R-tauopathy resulting from microtubule-associated protein tau (MAPT) pathology[@Litvan_2017]. Key features include:
- Neurofibrillary tangles: Composed of hyperphosphorylated tau protein
- Globose neurofibrillary tangles: Particularly in the brainstem
- Tufted astrocytes: Astrocytic tau pathology
- Neuronal loss: Particularly in the substantia nigra, subthalamic nucleus, and pallidum
Corticobasal Degeneration (CBD)
CBD is another 4R-tauopathy presenting with asymmetric cortical and extrapyramidal features[@Armstrong_2020]:
- Cortical atrophy: Especially in parietal and frontal regions
- Nigral degeneration: Dopaminergic neuron loss
- Astrocytic plaques: Characteristic CBD pathology
- Ballooned neurons: Cortical involvement
Frontotemporal Lobar Degeneration (FTLD)
FTLD encompasses a heterogeneous group of disorders with frontal and temporal lobe degeneration[@Rohrer_2011]. Many cases show tau pathology (FTLD-tau) while others demonstrate TDP-43 pathology (FTLD-TDP).
Objectives
Primary Objectives
Establish a Centralized Biobank: Create a well-characterized repository of biospecimens from patients with PSP, CBD, CBS, and related disorders
Enable Genetic Studies: Support genetic and genomic analyses to identify:
- Risk factors for disease development
- Modifier genes affecting progression
- Pathogenic variants in known causal genes[@Boxer_2020]
Advance Biomarker Development: Facilitate identification and validation of biomarkers for:
- Early diagnosis
- Disease progression tracking
- Treatment response monitoring[@Chen_2018]
Support Therapeutic Development: Create resources for:
- Target validation studies
- Clinical trial planning
- Patient stratification[@Boxer_2023]
Secondary Objectives
- Characterize genotype-phenotype correlations
- Support cross-institutional collaboration
- Enable development of cellular and animal models
Sample Collection Protocol
Blood Collection
| Sample Type | Volume | Processing | Storage |
|-------------|--------|------------|---------|
| EDTA whole blood | 10 ml | DNA extraction | -80°C |
| Serum | 10 ml | Centrifugation, aliquot | -80°C |
| Plasma (EDTA) | 10 ml | Centrifugation, aliquot | -80°C |
| PAXgene RNA | 2.5 ml | RNA extraction | -80°C |
Cerebrospinal Fluid Collection
CSF collection follows standardized protocols to minimize variability:
- Lumbar puncture: Standard atraumatic technique
- Collection tubes: Polypropylene, pre-chilled
- Processing: Centrifugation within 1 hour, aliquot
- Storage: -80°C, avoid repeated freeze-thaw
Skin Fibroblast Collection
In selected cases, skin biopsies are collected:
- Site: Upper arm or forearm
- Method: 3mm punch biopsy
- Culture: Fibroblast expansion in standard media
- Storage: Liquid nitrogen, passage 3-5
Clinical Data Repository
Alongside biospecimens, the repository maintains:
- Standardized clinical assessments
- Disease progression data
- Treatment history
- Family history information
Research Applications
Genetic Studies
The repository enables comprehensive genetic analyses:
- Whole genome sequencing: Identification of rare variants
- Exome sequencing: Focused variant discovery
- Genome-wide association studies (GWAS): Risk factor identification
- Gene expression studies: Transcriptomic profiling
Biomarker Research
Fluid Biomarkers
Biospecimens support biomarker discovery and validation[@Chen_2018]:
| Biomarker | Source | Clinical Application |
|-----------|--------|----------------------|
| Neurofilament light chain (NfL) | CSF, plasma | Disease progression[@Benussi_2022] |
| p-tau181/217/231 | CSF, plasma | Diagnostic specificity |
| Total tau | CSF | Neurodegeneration marker |
| Beta-amyloid | CSF | AD comorbidity screening |
| Alpha-synuclein | CSF, plasma | Lewy body pathology |
Imaging Biomarkers
The repository is linked with neuroimaging studies[@Irwin_2018]:
- MRI volumetric analysis
- PET tau imaging
- Diffusion tensor imaging
- Metabolic imaging (FDG-PET)
Disease Mechanism Studies
Biospecimens enable mechanistic research:
- Cellular models: Fibroblast-derived iPSC neurons
- Protein studies: Tau isoform analysis
- RNA studies: Gene expression profiling
- Metabolomic studies: Metabolic dysfunction
Significance for Precision Medicine
Diagnostic Precision
Well-characterized biospecimens enable:
- Differentiation between tauopathies
- Identification of mimics
- Development of diagnostic algorithms
Prognostic Precision
Natural history data support:
- Progression rate prediction
- Clinical trial endpoint selection
- Patient counseling
Therapeutic Precision
The repository enables:
- Biomarker-driven patient selection
- Target engagement studies
- Treatment response monitoring[@Boxer_2023]
Eligibility Criteria
Inclusion Criteria
Diagnosis: Confirmed or suspected diagnosis of:
- Progressive Supranuclear Palsy (any variant)
- Corticobasal Syndrome
- Corticobasal Degeneration
- Frontotemporal Lobar Degeneration with tau pathology
Age: Any age
Ability to Donate Biospecimens:
- Capacity to provide informed consent
- Able to undergo lumbar puncture (for CSF)
- Able to provide blood samples
Consent: Willingness to consent to:
- Long-term sample storage
- Data sharing with researchers
- Future research use
Exclusion Criteria
Medical conditions precluding biospecimen collection
Known bleeding disorders
Current participation in interventional trials
Other neurological conditions that could confound interpretationCTSA Program Integration
Network Resources
The study operates through the NIH Clinical and Translational Science Awards (CTSA) program, providing:
- Multi-site coordination: Standardized protocols across institutions
- Regulatory infrastructure: IRB oversight and compliance
- Biostatistics support: Data analysis expertise
- Community engagement: Patient outreach and recruitment
Collaborative Research
The repository supports:
- Multi-center studies: Pooled analyses
- International partnerships: Global research coordination
- Industry collaborations: Therapeutic development
- Patient advocacy engagement: Research priorities
Impact on Research
Advancing Understanding
The repository has contributed to advances in:
- Tau biology and propagation mechanisms
- Biomarker discovery and validation
- Clinical trial design
- Disease classification
Enabling Therapeutic Development
For clinical trials[@Boxer_2023]:
- Patient recruitment: Well-characterized cohorts
- Biomarker endpoints: Validated fluid markers
- Natural history: Progression rate data
- Target validation: Mechanistic studies
See Also
- [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy) — Primary disease
- [Corticobasal Degeneration](/diseases/corticobasal-degeneration) — Related disorder
- [Frontotemporal Lobar Degeneration](/diseases/frontotemporal-disease) — Related disorder
- [Tau Protein](/proteins/tau) — Pathological protein
- [MAPT Gene](/genes/mapt) — Tau gene
- [Neurofilament Light Chain](/biomarkers/neurofilament-light-chain) — Biomarker
- [Fluid Biomarkers Overview](/biomarkers/fluid-biomarkers) — Related biomarkers
External Links
- [ClinicalTrials.gov NCT05067192](https://clinicaltrials.gov/study/NCT05067192)
- [NIH CTSA Program](https://ctsa.ncats.nih.gov/)
- [CurePSP Foundation](https://www.psp.org/)
- [University of Pennsylvania PSP Research Center](https://www.penn neurology.org/)
Related Pages
- [CBS/PSP Genetic Architecture
- [PSP Genetic Variants](/diseases/psp-genetic-variants)
- [CurePSP Genetics Program](/clinical-trials/curepsp-genetics-program)
- 4R-Tauopathies Overview
- Neurodegenerative Disease Biomarkers
- Biobanking in Neurodegeneration](/diseases/progressive-supranuclear-palsy)## References
[ClinicalTrials.gov NCT05067192](https://clinicaltrials.gov/study/NCT05067192)[@nih]
[Boxer et al., FTD and related disorders (2020)](https://pubmed.ncbi.nlm.nih.gov/32092166/)[@Boxer_2020]
[Litvan et al., Clinical diagnostic criteria for PSP (2017)](https://pubmed.ncbi.nlm.nih.gov/28327879/)[@Litvan_2017]
[Armstrong et al., Clinical criteria for CBS (2020)](https://pubmed.ncbi.nlm.nih.gov/32128918/)[@Armstrong_2020]
[Benussi et al., Neurofilament light chain as biomarker (2022)](https://pubmed.ncbi.nlm.nih.gov/35499099/)[@Benussi_2022]
[Chen et al., Fluid biomarkers in neurodegenerative disease (2018)](https://pubmed.ncbi.nlm.nih.gov/30148620/)[@Chen_2018]
[Irwin et al., Neuroimaging biomarkers (2018)](https://pubmed.ncbi.nlm.nih.gov/29068454/)[@Irwin_2018]
[Rohrer et al., Clinical features of FTD (2011)](https://pubmed.ncbi.nlm.nih.gov/21047878/)[@Rohrer_2011]
[Williams et al., Tauopathies: classification (2021)](https://pubmed.ncbi.nlm.nih.gov/34599652/)[@Williams_2021]
[Kantarci et al., Biomarkers for tauopathies (2022)](https://pubmed.ncbi.nlm.nih.gov/35115661/)[@Kantarci_2022]
[McGough et al., Update on biomarkers (2023)](https://pubmed.ncbi.nlm.nih.gov/37526723/)[@McGough_2023]
[Boxer et al., Clinical trials in FTD (2023)](https://pubmed.ncbi.nlm.nih.gov/37153892/)[@Boxer_2023]
[Dickson et al., Neuropathology of tauopathies (2022)](https://pubmed.ncbi.nlm.nih.gov/35094189/)[@Dickson_2022]
[Kovacs et al., Biomarker validation in tauopathies (2021)](https://pubmed.ncbi.nlm.nih.gov/34596834/)[@Kovacs_2021]