LRRK2 (Leucine-Rich Repeat Kinase 2) Parkinson's Disease Fingerprint (NEU-PD)

LRRK2 Associated Parkinson's Disease: Definition of a Clinical, Molecular and Neurophysiological Fingerprint

The goal of this interventional monocentric study is to identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis and deep clinical phenotyping. Patients who meet the inclusion criteria, after signing the informed consent form will be clinically evaluated by a neurologist expert in movement disorders. Eventually, patients will undergo a blood sample collection, a brain MRI, and a high density EEG. All data will be collected using an ad hoc electronic Case Report Form (CRF) developed for the study

Study Overview

• Status: Not yet recruiting
• Conditions: LRRK2; Parkinsons Disease (PD)
• Intervention / Treatment: Diagnostic test: The interventions of the study are the study of blood biomarkers and neuroimaging and neurophysiological data

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Giulia Di Lazzaro, MD, PhD, Neurologist; Phone Number: +39 3333310889; Email: giulia.dilazzaro@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age 30-80 years,
• clinically established diagnosis of PD according to the Movement Disorders Society (MDS) diagnostic criteria,
• Hoehn & Yahr (H&Y) stage between 1 and 3,
• 10 patients with a LRRK2 associated parkinsonism and 10 with sporadic PD tested with a NGS panel and MLPA for PD associated genes,
• ability to provide informed consent.

Exclusion Criteria:

• Active or history of other neurological disorders,
• active infectious disease or history within the previous 4 weeks,
• continuative therapy (at least 1 week) with NSAIDs or steroids within the previous 12 weeks,
• active malignancy, autoinflammatory or autoimmune diseases or history within the previous 3 years;
• alcohol or drug abuse or dependence
• any contraindication to the execution of the MRI (including claustrophobia).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients who meet the inclusion criteria; This is a single arm study. All enrolled patients will receive the same interventions throughout the study.	Diagnostic test: The interventions of the study are the study of blood biomarkers and neuroimaging and neurophysiological data; Blood sample collection and markers analysis; Brain 1.5 T MRI; High density EEG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.	Movement Disorders Society- Unified PD Rating Scale (MDS-UPDRS). The scoring basis is 0 to 4. The total score across all parts ranges from 0 (no disability) to 260 (total disability). The higher the score, the more advanced or severe the symptoms are.	Through the study completion, about 3 years
2) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.	The Hoehn and Yahr (H&Y) scale. Stage 0: No signs of disease. Stage 1: Unilateral (one-sided) disease involvement only, with minimal or no functional impairment. Stage 1.5: Unilateral plus axial (neck/torso) involvement. Stage 2: Bilateral or midline involvement, without impairment of balance. Stage 2.5: Mild bilateral disease, with recovery on the clinical "pull test" (balance reflex assessment). Stage 3: Mild to moderate bilateral disease; some postural instability, but the patient remains physically independent. Stage 4: Severe disability; however, the patient is still able to walk or stand unassisted. Stage 5: Wheelchair-bound or bedridden unless aided.	Through the study completion, about 3 years
3) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.	Unified dyskinesia rating scale (UDysRS). Scoring uses a 0 to 4 Likert-type scale, where higher scores indicate greater dyskinesia severity and impairment.	Through the study completion, about 3 years
4) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.	Non-Motor symptoms scale (NMSS). Each of the 30 items is scored by multiplying its severity (0-3) by its frequency (1-4), yielding a possible subscore from 0-12 per item and a total score ranging from 0 to 360. Severity: 0 = None, 1 = Mild: symptoms present but causes little distress or disturbance to patient; 2 = Moderate: some distress or disturbance to patient; 3 = Severe: major source of distress or disturbance to patient. Frequency: 1 = Rarely (<1/wk); 2 = Often (1/wk); 3 = Frequent (several times per week); 4 = Very Frequent (daily or all the time).	Through the study completion, about 3 years
5) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.	Montreal Cognitive Assessment (MoCA). Total Score: 30 points possible. Normal Result: A score of 26 or higher is typically considered normal.	Through the study completion, about 3 years
6) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.	Mini Mental status evaluation (MMSE). While the scoring is out of 30 points, results are often categorized to gauge severity: 25-30: Normal cognitive function. 21-24: Mild cognitive impairment. 10-20: Moderate cognitive impairment. Below 10: Severe cognitive impairment.	Through the study completion, about 3 years
7) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.	Questionnaire for impulsive-compulsive disorders (QUIP). A rating scale measuring symptom severity. It evaluates 4 primary impulse control disorders (gambling, sexual, buying, eating) and related behaviors, scoring them from 0 to 16 based on thoughts, urges, and difficulty to control.	Through the study completion, about 3 years
8) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.	Beck depression inventory (BDI). Each statement is assigned a value from 0 to 3. The scores for all 21 questions are added together to produce a total score between 0 and 63. Total score: 0 to 13: Minimal depression 14 to 19: Mild depression 20 to 28: Moderate depression 29 to 63: Severe depression	Through the study completion, about 3 years
9) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping.	Beck Anxiety Inventory (BAI). Scoring basis: ranging from 0 (not at all) to 3 (severely). Total score: 0-7: Minimal anxiety 8-15: Mild anxiety 16-25: Moderate anxiety 26-63: Severe anxiety	Through the study completion, about 3 years
10) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping	Molecular markers assessment: A panel of pro- and anti-inflammatory mediators will be analysed (IL1-b, TNFa, IFNg, IL4, IL5, IL6, IL17, IL10) along with Neurofilament light chain. The unit of measure is pg/mL.	Through the study completion, about 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1) Mechanistic Modeling of LRRK2-Associated Parkinson's Disease	IDENTIFY relevant data features (months 12-36). This task seeks to map large-scale brain dynamics (EEG-derived metrics) to symptoms-related changes in idiopathic PD (Parkinson's Disease) vs LRRK2-PD, before and after dopaminergic therapy. The success of task one will be evaluated on the predictive power of the EEG-derived metrics to distinguish ON/OFF, LRRK2/Idiopathic patients and to predict clinical symptoms.	Through study completion, about 3 years
2) Mechanistic Modeling of LRRK2-Associated Parkinson's Disease	PREDICT such changes using patient-specific in silico models (months 12-36). This task aims to develop a mechanistic model that simulates the effects of changes in Protocol NEU-PD V.1.0 of 05th May 2026 Pag. 7 | 10 activities in the SPNs (i.e. firing rate, spontaneous excitability - glutamatergic activity) on the whole-brain dynamics at the individual level. A brain model consists of a set of equations that encapsulate pathophysiological knowledge and patient-specific features. Solving the model generates patient-specific synthetic brain data. In these models the brain is parceled in a set of regions based on anatomo-functional atlases. Each node is informed with specific features that determine the local activities. In-silico simulations allow to infer how large-scale dynamics emerge from the interaction of local properties. The success of this task will be measured by the model's ability to reproduce conditionspecific (LRRK2/PD) EEG signal features.	Through the study completion, about 3 years

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: June 26, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 10, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Investigative Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Imaging; Diagnostic Techniques, Neurological; Neuroimaging
• Other Study ID Numbers: 27556

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data gathered in accordance with the protocol will be inserted in the eCRF (electronic Case Report Form) made for this study. Analyzed data will be shared through publications.
• IPD Sharing Time Frame: The IPD and supporting documents will be available from the start of the study (around Sep 2026) for the duration of the study (3years)
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No