The New York Stem Cell Foundation (NYSCF) Scientific Discovery Biobank (NCT06203106) is a large-scale observational repository established to collect and characterize biospecimens from patients with neurodegenerative diseases. This biobank represents one of the most comprehensive stem cell resources for neurodegenerative disease research globally, enabling researchers worldwide to access patient-derived induced pluripotent stem cell (iPSC) lines for disease modeling, drug screening, and mechanistic studies.
- NCT Number: NCT06203106
- Status: Recruiting
- Study Type: Observational/Biobank
- Conditions: Progressive Supranuclear Galsy (PSP), Parkinson's Disease (PD), Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), Corticobasal Syndrome (CBS), Huntington's Disease (HD)
- Sponsor: The New York Stem Cell Foundation
- Sites: New York, NY and collaborating academic medical centers
- Enrollment Target: Not specified (ongoing recruitment)
¶ Background and Rationale
Neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, PSP, ALS, and others share common pathophysiological features including protein aggregation, mitochondrial dysfunction, neuroinflammation, and progressive neuronal loss. However, the mechanistic basis for these diseases remains incompletely understood, partly due to the limited availability of relevant human cellular models.
Patient-derived iPSCs offer a transformative approach to neurodegenerative disease research by enabling researchers to:
- Generate patient-specific cellular models that retain the genetic background of individual donors
- Differentiate iPSCs into disease-relevant cell types including dopaminergic neurons (for PD), motor neurons (for ALS), and cortical neurons (for AD)
- Study disease mechanisms in a human context that is not fully recapitulated in animal models
- Perform high-throughput drug screening on human disease-relevant cells
- Develop personalized medicine approaches based on individual patient genetics
The NYSCF biobank addresses the critical need for standardized, well-characterized iPSC lines from patients with diverse neurodegenerative conditions. By providing access to these valuable resources, the NYSCF accelerates the pace of discovery research and facilitates the development of novel therapeutic interventions.
- Biospecimen Collection: Collect blood samples from patients with clinically diagnosed neurodegenerative diseases
- iPSC Generation: Generate and characterize high-quality iPSC lines from patient-derived blood cells
- Clinical Phenotyping: Document detailed clinical phenotypes including disease severity, progression rate, and treatment history
- Resource Distribution: Provide iPSC lines and associated clinical data to qualified researchers worldwide
- Genomic Characterization: Perform whole genome sequencing or targeted genetic panels on donor samples
- Phenotypic Characterization: Characterize iPSC-derived cells for disease-relevant markers and functional properties
- Longitudinal Follow-up: Track clinical outcomes over time to correlate genotype with phenotype
- Biobank Expansion: Continuously expand the collection to include additional disease subtypes and genetic variants
¶ Sample Collection and Processing
| Specimen Type |
Purpose |
Processing |
| Peripheral Blood Mononuclear Cells (PBMCs) |
Reprogramming to iPSCs |
Ficoll density gradient separation |
| Plasma |
Biomarker studies |
Centrifugation and aliquoting |
| Serum |
Protein biomarker analysis |
Clotting and centrifugation |
| DNA |
Genetic analysis |
Extracted from PBMCs |
| RNA |
Gene expression studies |
Stored in RNA preservation buffers |
The NYSCF employs a non-integrative reprogramming methodology to generate iPSC lines. This approach utilizes:
- Sendai virus vectors encoding OCT4, SOX2, KLF4, and c-MYC (the Yamanaka factors)
- Feeder-free culture conditions on defined matrix substrates
- Automated quality control including sterility testing, mycoplasma screening, and pluripotency verification
The resulting iPSC lines are carefully characterized to ensure:
- Normal karyotype (absence of chromosomal abnormalities)
- Pluripotency marker expression (TRA-1-60, TRA-1-81, SSEA-4, OCT4)
- Ability to differentiate into all three germ layers (ectoderm, mesoderm, endoderm)
The iPSC lines in the NYSCF biobank have been used to create disease models for multiple neurodegenerative conditions:
Parkinson's Disease Models:
- iPSC-derived dopaminergic neurons from PD patients have revealed disease-specific phenotypes including:
- Reduced neurite outgrowth and branching
- Increased susceptibility to oxidative stress
- Mitochondrial dysfunction and reduced ATP production
- Alpha-synuclein accumulation and aggregation
- Studies comparing monozygotic twins discordant for PD have identified epigenetic and gene expression differences that may underlie disease susceptibility
Alzheimer's Disease Models:
- NYSCF iPSC lines from patients with familial AD mutations (PSEN1, PSEN2, APP) have enabled:
- Identification of disease-specific molecular subtypes through RNA sequencing
- Demonstration of amyloid-beta and tau pathology in patient-derived neurons
- CRISPR/Cas9-mediated correction of mutations with reversal of phenotypes
- Studies of autophagy and mitophagy defects in AD neurons
- Characterization of PSEN1 familial AD neural progenitors
Amyotrophic Lateral Sclerosis Models:
- Motor neurons derived from ALS patient iPSCs have been used to study:
- TDP-43 proteinopathy
- RNA metabolism defects
- Mitochondrial dysfunction
- Axonal transport deficits
¶ Drug Discovery and Screening
The NYSCF biobank supports high-throughput drug screening campaigns by providing:
- Well-characterized cell lines representing diverse genetic backgrounds
- Differentiated cells at defined developmental stages
- Standardized protocols for differentiation and assay development
- Access to clinical data enabling stratification of cell lines by disease phenotype
Researchers have employed NYSCF iPSC lines to investigate fundamental mechanisms of neurodegeneration:
- Neuroinflammation: Studies on patient-derived astrocytes and microglia have revealed disease-specific inflammatory signatures
- Protein aggregation: Direct visualization of alpha-synuclein, tau, and TDP-43 aggregation in living neurons
- Mitochondrial biology: Assessment of mitochondrial function using Seahorse extracellular flux analysis
- Calcium signaling: Investigation of calcium dysregulation as a common pathogenic mechanism
- Age: 18-85 years
- Diagnosis: Confirmed diagnosis of a qualifying neurodegenerative disease by a board-certified neurologist
- Capacity to provide informed consent: Ability to understand and voluntarily sign the consent form
- Willingness to provide blood sample: Agreeable to venipuncture for biospecimen collection
- Previous iPSC generation: Individuals who have already participated in iPSC reprogramming studies
- Active malignancy: Current diagnosis of cancer (except non-melanoma skin cancer)
- Active infection: Current serious infection including HIV, hepatitis B, or hepatitis C
- Pregnancy: Current pregnancy or planning pregnancy within the study period
¶ Significance and Impact
The NYSCF biobank has established itself as a critical resource for the neurodegenerative disease research community:
- Over 1,000 patient-derived iPSC lines representing multiple disease categories
- Distribution to over 100 research institutions worldwide
- Contributions to hundreds of peer-reviewed publications advancing understanding of neurodegenerative disease mechanisms
- Partnership with pharmaceutical companies for drug discovery and validation
The biobank has enabled numerous scientific discoveries including:
- Identification of novel disease mechanisms through comparative studies of patient-derived cells
- Validation of therapeutic targets using human cellular models
- Biomarker discovery through proteomic and metabolomic profiling
- Personalized medicine approaches based on individual patient genetics
The NYSCF has established partnerships with:
- Academic medical centers specializing in movement disorders and dementia
- Industry partners for drug discovery collaborations
- International stem cell repositories for resource sharing
- Patient advocacy organizations for recruitment and outreach
¶ Data Access and Sharing
Researchers interested in obtaining iPSC lines from the NYSCF biobank must:
- Submit a research proposal describing the scientific rationale and experimental plan
- Obtain institutional approval (IRB or ethics committee)
- Complete a materials transfer agreement (MTA)
- Pay applicable fees for cell lines and shipping
The NYSCF provides the following data with each iPSC line:
| Data Type |
Description |
Format |
| Clinical Data |
Diagnosis, disease duration, medications, clinical scores |
De-identified CSV |
| Genetic Data |
Known disease mutations, APOE genotype |
VCF or CSV |
| Phenotypic Data |
Differentiation efficiency, marker expression |
PDF reports |
| Quality Control |
Mycoplasma status, karyotype, sterility |
Certificate of analysis |
¶ Similar Biobanks and Registries
- NIH PSP Biospecimen Repository: Collection of biospecimens from PSP patients
- Michael J. Fox Foundation Parkinson's Progression Markers Initiative (PPMI): Longitudinal PD cohort with biospecimens
- UPenn Neurodegenerative Disease Repository: iPSC lines from AD, PD, and FTD patients
- Coriell Institute for Medical Research: Human genetic cell repository