LRRK2, Parkinsons Disease (PD)
Conditions
Brief summary
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
Interventions
DIAGNOSTIC_TESTThe 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
Sponsors
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Intervention model description
The study is considered interventional, as the interventions of the study which are the study of blood biomarkers and neuroimaging and neurophysiological data, do not enter in normal clinical practice.
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping. | Through the study completion, about 3 years | 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. |
| 2) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping. | Through the study completion, about 3 years | 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. |
| 3) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping. | Through the study completion, about 3 years | Unified dyskinesia rating scale (UDysRS). Scoring uses a 0 to 4 Likert-type scale, where higher scores indicate greater dyskinesia severity and impairment. |
| 4) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping. | Through the study completion, about 3 years | 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). |
| 5) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping. | Through the study completion, about 3 years | Montreal Cognitive Assessment (MoCA). Total Score: 30 points possible. Normal Result: A score of 26 or higher is typically considered normal. |
| 6) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping. | Through the study completion, about 3 years | 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. |
| 7) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping. | Through the study completion, about 3 years | 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. |
| 8) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping. | Through the study completion, about 3 years | 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 |
| 9) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping. | Through the study completion, about 3 years | 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 |
| 10) To identify molecular and clinical markers of LRRK2-related Parkinson's disease through blood markers analysis, deep clinical phenotyping | Through the study completion, about 3 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1) Mechanistic Modeling of LRRK2-Associated Parkinson's Disease | Through study completion, about 3 years | 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. |
| 2) Mechanistic Modeling of LRRK2-Associated Parkinson's Disease | Through the study completion, about 3 years | 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. |
Contacts
CONTACTGiulia Di Lazzaro, MD, PhD, Neurologist
Outcome results
None listed