STEM-Parkinson's Disease

Inclusion Criteria:

• Adult participants (aged 18 - 85 years inclusive)

• Diagnosed with Parkinson's disease according to the UK Brain Bank Criteria (allowingfor an exclusion in Step 2 for "more than one affected relative").

• Demonstrates a sustained, positive response to dopamine replacement therapies (DRTs) (e.g., levodopa, dopamine agonists or monoamine oxidase inhibitors) defined aseither good or excellent responses (50-100%) for at least one year or moderateresponses (30-49)% for at least three years prior to screen.

• Participant-reported or clinician-investigator-determined limitation, based onknowledge of medical history, to one or more activities of daily living (e.g.,writing, walking, bathing, dressing, eating, toileting, etc.)

• Able and willing to consent to participate in the study.

• Willing and able to comply with study requirements.

• Participants and investigators must expect that the participant will be able toremain on a stable regimen of concomitant therapies used for the management of PDmotor and non-motor symptoms and not to introduce new medications used to treatmotor or non-motor symptoms associated with PD during the study.

• Have at minimum a moderate burden of non-motor symptoms associated with Parkinson'sdisease (i.e., MDS-UPDRS part Ia and part Ib summed total score ≥ 9) at study screento avoid floor effects for the primary endpoint (MDS-NMS).

• The principal investigator or designee must have confidence in the participant'sability to reliably use the TNM™ device, understand the assessments (provided inEnglish only) and to complete the assessment battery within a given on-state period.

• Have a study partner (defined as someone who sees the participant for more than onehour a day, 3 times per week) that is willing to consent and participate in thetrial.

• Have capabilities to use and access smartphones and or tablets for the collection ofsome study data and/or tablets or computers for access to telemedicine platforms.

• Must be willing to answer questions related to sexual interest, arousal, andperformance in an interview with study staff.

Exclusion Criteria:

• Participant anticipates being unable to attend all visits and complete all studyactivities.

• Women of child-bearing potential who are pregnant or plan to become pregnant duringthe course of the study trial. Women of child-bearing potential , who are notabstinent or exclusively in same sex relationships must:

1. Test negative for pregnancy as indicated by a negative urine pregnancy test

2. Agree to use an approved contraception method for the entirety of the trial

• Have a history or prior diagnosis of dementia or or adjusted score ≤ 20 on theMontreal Cognitive Assessment (MoCA) at the screening visit

• Have experienced a myocardial infarction, angina, or stroke within the past 12months, or a transient ischemic attack within the past 6 months.

• Are receiving deep brain stimulation therapy.

• Are treated with a pump for continuous delivery of dopamine replacement medication.

• Have received MRI guided high intensity focused ultrasound within the past 12months.

• Experience frequent falls. (defined as 2 or more falls in the past month related toParkinson's disease). Parkinson's falls are defined as falls associated withbradykinesia, freezing, turning, change in posture and postural dizziness and do notinclude accidental falls.

• Work night shifts

• Use a hearing aid that is implanted or that cannot be easily removed and replaced.

• Has any significant co-morbidity or illness which in the opinion of the investigatorwould prevent safe participation in the study, compliance with protocol requirementsor which presents with symptoms that are also common in PD.

• Demonstrate suicidality at screening (scores ≥ 4 on the C-SSRS Baseline in section "Suicidal Ideation" (In the past Month)). Participants that respond affirmatively toquestion 4 or 5 (In the past Month) should receive a referral for mental healthcounseling according to local site regulations and standards

• Use a hearing aid that is implanted or that cannot be easily removed and replaced

• Have a cochlear implant or myringotomy tubes

• Have chronic that has been ongoing for at least 3 months and causes significantimpairment of communication and/or impairment of activities of daily living.

• Have previously been diagnosed with traumatic brain injury with ongoing sequalae.

• Have been diagnosed with a co-morbid neurological disorder that may present withsymptoms overlapping with PD (e.g., stroke, brain tumor, epilepsy, Alzheimer'sdisease, multiple sclerosis, amyotrophic lateral sclerosis, atypical Parkinsonism oraneurysm)

• Have been previously diagnosed with either clinically meaningful central vestibulardysfunction (lifetime) or have experienced clinically meaningful peripheralvestibular dysfunction within the last 12 months. For this purpose, clinicallymeaningful is defined as vestibular dysfunction which causes at least a minimalimpairment in the individual activities of daily living (e.g., dressing, bathing,preparing food, conducting household chores, work or recreational activities).

• In the Investigator's opinion, currently abuse alcohol, abuse drugs (includinglegal, illegal or prescribed drugs) or have a history of alcohol or drug dependencywithin the past 5 years or use any drugs excluded as noted in the ExcludedMedications List

• Have unresolved complications from a previous surgical procedure at the baselinevisits, such as swelling or persistent pain, that requires medical intervention.

• Have active ear infections, perforated tympanic membrane or labyrinthitis, asidentified by a general ear examination performed by medically qualifiedInvestigators.

• Have a recent history of frequent ear infections (≥ 1 per year over the past twoyears)

• Are currently enrolled or have participated in another interventional clinical trialwithin the last 30 days.

• Have had eye surgery within the previous three months or ear surgery within theprevious six months.

• Have planned surgery scheduled to occur during the study that requires sedationand/or would typically be followed with a prescription for pain management.

• Have had eye surgery within the previous three months or ear surgery within theprevious six months.