Parkinson's Disease Progression Study

Inclusion criteria:

1. Aged ≥18 years to ≤85 years of age.

2. Body mass index (BMI) ≥18 to 40 kg/m2.

3. In adequate health based on medical history and physical examination (other than PD)undertaken following standard care procedures and presenting minimal risk for takingpart in the study, per investigator assessment.

4. Participant or caregiver has demonstrated ability to perform satisfactory in-clinicand remote procedures during the screening period.

5. Clinically established PD, consistent with Postuma et al (Mov Disord; 2015).

6. H&Y stage 1 or 2.

Exclusion criteria:

1. Unable to commit to 12 months of data collection.

2. Planning to enroll in a clinical trial for disease modifying therapy that willoverlap with the duration of this study.

3. Parkinsonism due to drugs(s) and or toxin(s).

4. Increased risk of falling, defined as >6 falls within the 12 months prior toscreening.

5. Urine drug screen positive for opiates, phencyclidine (PCP), cocaine, oramphetamines.

6. Regular binge drinking, defined as ≥4 alcoholic drinks for women or ≥5 alcoholicdrinks for men, per investigator assessment.

7. Current or recent (within 6 months prior to screening) diagnosis of a moderate orsevere substance use disorder (excluding caffeine) according to Diagnostic andStatistical Manual of Mental Disorders-5 criteria. Note that nicotine use disorderis an exclusion criterion only if it has an effect on sleep (i.e., a participant whoroutinely awakens at night to smoke), and medical or recreational marijuana is notincluded in this exclusion criterion.

8. Severe cardiopulmonary, hepatic, renal, or musculoskeletal disease such thatactivities of daily living are adversely impacted.

9. History of neoplastic disease, with the exception of (1) an adequately treated basalcell carcinoma or carcinoma in situ of the cervix; (2) other malignancies which havebeen successfully treated >5 years prior to screening without evidence ofrecurrence.

10. Currently participating in another clinical trial, or previous participation in aclinical trial in which an investigational product was received within 30 days priorto screening or within at least 5 half-lives of the investigational product.

11. Current or planned pregnancy.

12. History of seizures, epilepsy, stroke, multiple sclerosis, or traumatic brain injury (other than mild traumatic brain injury).

13. Intracranial metallic or magnetic devices, such as a cochlear implant or deep brainstimulator.

14. Implanted active device, such as a pacemaker or defibrillator.

15. History of gene therapy, intracranial antisense oligonucleotide treatment, celltransplantation, or experimental brain surgery.

16. Current untreated or unstable depressive disorder or a serious mood disorderrequiring hospitalization.

17. Other primary degenerative dementia or neurodegenerative conditions outside of thespecific basket in which the participant is enrolled, where applicable.

18. Other uncontrolled infectious, metabolic, or systemic diseases affecting the centralnervous system, such as syphilis, hypothyroidism, vitamin B12 or folate deficiency,and other laboratory values.

19. Any other medical, psychiatric, or social condition that, in the opinion of theinvestigator, is likely to unfavorably alter the risk-benefit of participation, tointerfere with protocol compliance, or to confound safety or efficacy assessments.

Additional exclusion criterion for the subset of treatment-naive participants only:

1. No prior treatment to manage motor symptoms of PD; note that brief periods ofdopaminergic therapy administered to establish diagnosis are not grounds forexclusion.