National Parkinson's biobank with whole genome sequencing and patient-derived stem-cell testing

Implementing a National Biobank of Genetic, Sporadic and Prodromic Parkinson's Disease With Whole Genome Analysis and Functional Assessment of Polygenic Inheritance by iPSC Technology

This project will test whether combining whole genome sequencing and patient-derived stem cells can help find rare genetic changes linked to Parkinson's disease and REM sleep behavior disorder.

Quick facts

• Study type: Observational
• Enrollment: 230 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: IRCCS San Raffaele (Academic / other)
• Locations: 1 site (Milan, Italy)
• Trial ID: NCT05721911 on ClinicalTrials.gov

What this trial studies

This multicenter observational project will create a standardized national biobank of blood, DNA, and cellular samples from people with Parkinson's disease (PD), REM sleep behavior disorder (RBD), and healthy controls. Teams will harmonize clinical reporting and sample collection across centers, recruit additional participants, and perform whole genome sequencing on a selected cohort (about 200 PD cases negative for known PD gene mutations) as well as on RBD patients. Investigators will generate and quality-control induced pluripotent stem cell (iPSC) lines from patient blood and use gene editing to test the functional effects of co-inherited rare coding variants as a potential polygenic driver of sporadic PD. The biobank and validated iPSC lines will be made available to the scientific community to support further research.

Who should consider this trial

Good fit: Ideal participants are adults with sporadic Parkinson's disease who meet clinical diagnostic criteria (at least two cardinal signs, including tremor or bradykinesia), people with idiopathic REM sleep behavior disorder per ICSD-3, and healthy controls (often spouses).

Not a fit: People with atypical parkinsonism, known monogenic Parkinson's mutations, major psychiatric disorders, or other neurodegenerative diseases are unlikely to gain direct benefit from this observational genetic and iPSC-focused project.

Why it matters

Potential benefit: If successful, this could lead to earlier genetic diagnosis, better understanding of disease mechanisms, and identification of new targets for treatments.

How similar studies have performed: Whole genome sequencing and iPSC modeling have previously linked some rare variants to Parkinson's biology, but using gene-edited iPSCs to functionally test the combined impact of multiple rare variants as a polygenic mechanism is relatively novel.

Eligibility criteria

Inclusion Criteria PD patients:

* Presence of at least 2 of the 4 cardinal signs (tremor, rigidity, bradykinesia, onset asymmetric) one of which must be tremor or bradykinesia;
* Absence of atypical symptoms such as: i) early postural instability, freezing phenomena, cognitive impairment, hallucinations, pathological involuntary movements, vertical gaze paralysis; ii) confirmed causes of secondary parkinsonism (focal lesions, drugs, substances toxic);
* Documented response to L-dopa or dopamine agonist use (or lack of adequate therapeutic attempt with L-dopa or dopamine agonists).

Inclusion Criteria RBD patients:

• Subjects affected by idiopathic RBD that will be selected according to the most recent criteria international classification of sleep disorders (ICSD-3).

Exclusion Criteria:

* pre-existing psychiatric conditions;
* Neurodegenerative neurological diseases such as multiple sclerosis, lateral sclerosis amyotrophic, Alzheimer's, neuromuscular pathologies, epilepsy;
* diagnosis of dementia;
* depression;
* prolonged intake of anxiolytics, antidepressants, antipsychotics, hypnotic drugs, cognitive stimulants

Where this trial is running

Milan, Italy

• IRCCS San Raffaele — Milan, Italy, Italy (Recruiting)

Study contacts

• Principal investigator: Vania Broccoli, PhD — IRCCS San Raffaele
• Study coordinator: Vania Broccoli, PhD

Conditions Parkinson Disease; REM Sleep Behavior Disorder