movement disorder Parkinson's disease
Conditions
Interventions
None listed
Sponsors
Denali Therapeutics Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Groups A and B 1. Confirmed clinical diagnosis of Parkinson*s disease by a qualified neurologist, 2. Hoehn and Yahr stage I-IV, inclusive, 3. Group A: Confirmed mutation in the Leucine-rich repeat kinase 2 (LRRK2) gene of the following types: G2019S, I2020T, R1441G, R1441C, R1441H, N1437H or Y1699C. 4. Group B: Confirmed wild type Leucine-rich repeat kinase 2 (LRRK2) gene. 5. Male or female of 30-85 years of age at screening (inclusive). Group A patients may be as young as 25 years of age with Investigatory and Sponsor agreement. 6. Body mass index (BMI) between 18 and 35 kg/m2 (inclusive), and with a minimum weight of 50 kg at screening. 7. Able to speak, read, and understand study procedures in Dutch sufficiently to allow completion of all study assessments. 8. Mentally competent as assessed by the screening physician and *if deemed necessary- by the treating neurologist 9. Must understand and provide written informed consent prior to the initiation of any protocol-specific procedures. 10. Willing and able to maintain stable doses and regimens for all medications, herbal treatments, medical marijuana, dietary supplements and caffeine intake from the screening visit through the last study visit. 11. Willing and able to abstain from alcohol 48 hours prior to all study procedures at study visits 1 and 2.;Group C: 1. No clinical evidence or history of Parkinson disease 2. Male or female matched to a participant in Group A and/or Group B for gender, race, age (+/- 5 years) and BMI (+/- 3.5, with a minimum weight of 50 kg at screening). 3. Able to speak, read, and understand study procedures in Dutch sufficiently to allow completion of all study assessments. 4. Must understand and provide written informed consent prior to the initiation of any protocol-specific procedures. 5. Willing and able to maintain stable doses and regimens for all medications, herbal treatments, dietary supplements and caffeine intake from the screening visit through the last study visit. 6. Willing and able to abstain from alcohol 48 hours prior to all study procedures at study visits 1 and 2.
Exclusion criteria
Exclusion criteria: Groups A * C 1. Self-reported substance or alcohol dependence (excluding caffeine), and/or participated in a substance or alcohol rehabilitation program to treat substance or alcohol dependence within the past 6 months 2. History or presence of clinically significant or unstable abnormality as assessed by physical examination, medical history, 12-lead ECG, vital signs, or laboratory values, which in the opinion of the investigator would jeopardize the safety of the participant or the validity of the study results 3. Positive urine drug screen, except for medical marijuana which is permitted 4. Positive breath alcohol test. Participants with a positive result may be rescheduled at the investigator*s discretion 5. Groups A and B: Parkinson disease associated mutations in the GBA gene, as determined by genetic testing or documented before screening. 6. Group C only: first order relative with Parkinson disease 7. Females who have a positive serum or urine pregnancy test 8. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening 9. Hemoglobin level
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - LRRK2 phosphorylation (pS935, total LRRK2 and pS935/Total LRRK2 ratio) in 1. PBMCs 2. Whole blood 3. Neutrophils 4. Urine exosomes 5. CSF exosomes - Rab GTPase phosphorylation in 1. PBMCs 2. Whole blood 3. Neutrophils 4. Urine exosomes 5. CSF exosomes - Lipidomic, metabolomic and/or proteomic analysis of 1. CSF 2. Urine and/or 3. Plasma - CSF lysosomal enzyme activity 1. Cathepsin D, 2. Glucocerebrosidase - CSF alpha-synuclein 1. Total 2. pS129 and/or 3. Oligomeric alpha-synuclein - CSF and plasma cytokines (65-cytokine panel) - Cellular analyses of fibroblast cultures, e.g. lysosome imaging, immunohistochemistry for lysosome markers (LAMP1, LAMP2, etc), lysotracker, LRRK2pS935 and pRab10 immunoassays, LC/MS analysis, protein turnover analysis, and Lysosome enzyme activity assays. - Potential other parameters related to LRRK2 that become available | — |
Countries
Netherlands
Outcome results
None listed