Validation of α-synuclein Modifications in Parkinson's dIsoRder Evolution

Summary

Parkinson's disease (PD) presents a complex challenge due to its progressive neurodegenerative nature, affecting various bodily systems. Despite decades of research, understanding its onset and progression remains unclear, complicating early diagnosis and treatment. Recent advances in PD pathophysiology suggest promising treatments to slow disease progression, yet reversing cellular degeneration remains elusive. With novel therapies emerging, the need for early detection tools is urgent. However, validated biomarkers for PD diagnosis are lacking, relying on subjective scales like Hoehn and Yahr or costly medical imaging techniques. The accumulation of misfolded α-Synuclein (α-Syn) proteins in PD pathology has sparked interest, but defining diagnostic roles requires further investigation. Recent findings of α-Syn in neuronal-derived extracellular vesicles (NDEVs) from PD patients suggest a potential for novel diagnostic methods. Our proposed project, VαMPiRE, aims to conduct a longitudinal study involving 600 PD and 600 non-PD participants using a cluster-adjusted case-control methodology, to explore α-Syn isoforms and related biomarkers in NDEVs for early PD detection.

We plan to develop and validate an innovative in-vitro diagnostic (IVD) test capable of detecting PD's earliest stages and estimating disease prognosis and progression. Utilizing AI models to generate data analysis algorithms and collaboration with leading analytical laboratories and IVD manufacturers, we aim to ensure the reliability and feasibility of the developed prototype. Through consortium efforts, we envision licensing the generated intellectual property to drive the commercialization of our results.

Two round of blood sample extractions will be performed within a 24-month gap to PD participants and a single baseline for non-PD controls. All participants will be regularly followed up during this 24-month period to monitor disease evolution and treatment, and non-PD controls developing the disease will be part of a third cohort (expected to be around 24 subjects according to 4% incidence) that will confirm the sensitivity of the test in asymptomatic subjects. The unique aspect of the project is that we anticipate being able to detect theses 4% of non-PD participants that will go on to develop the disease, therefore demonstrating the value of these biomarkers to identify PD early.

The prototype will be validated for its discriminative capacity, using the first baseline set of PD and non-PD samples, and for its ability to detect the PD-progression comparing baseline and 24-months data plus blood samples.

Improved early screening could allow for 270,000 new cases of PD to be detected earlier, improve the disease management of 9.4 M people currently diagnosed of PD and avoid losing a total of 5.8 million disability adjusted life years (DALYs) by 2028 leading also the development of better treatments.

Conditions

• Parkinson Disease (PD)

Interventions

OTHER

Blood draw for the laboratory assessment

Participants' clinical histories will be reviewed at T0 (baseline) and T1 (24 months). They will also undergo a clinical assessment at T0 and T1. The assessments will be tailored based on whether the participant belongs to the PD or non-PD group, as outlined below: • MDS-UPDRS + H\&Y: Used to evaluate the neurological domain, applied to the PD group. • BERG: Used to assess balance and performance, applied to both PD and non-PD groups. • CIRS-G: Used to evaluate comorbidities, applied to both PD and non-PD groups. • PD-CRS: Used to assess cognitive function, applied to the PD group. • MMSE (temporal and spatial orientation only): Used to assess cognitive function, applied to both PD and non-PD groups. • PDQ-8: Used to evaluate quality of life, applied to the PD group. • PD-CFRS: Used for functional assessment, applied to the PD group. • GDS: Used to assess depression, applied to both PD and non-PD groups. Blood samples will be collected at T0 and T1, with 20 mL drawn per participant.

Sponsors & Collaborators

• Asociación Parkinson Madrid

  collaborator OTHER

• Aristotle University Of Thessaloniki

  collaborator OTHER

• Institute of Psychiatry and Neurology, Warsaw

  collaborator OTHER

• LINKCARE HEALTH SERVICES SL

  collaborator UNKNOWN

• ALMAWAVE SPA

  collaborator UNKNOWN

• European Brain Research Foundation

  collaborator UNKNOWN

• Casa di Cura IGEA

  lead OTHER

Principal Investigators

• Marco Feligioni, PHD · EBRI-European Brain Research Insitute

• Elda Judica, MD · Casa di Cura IGEA

Eligibility

Min Age

18 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-05-12

Primary Completion

2028-11-30

Completion

2029-04-30

Countries

• Greece
• Italy
• Poland
• Spain

Study Locations