LRRK2 and Other Novel Exosome Proteins in Parkinson's Disease

The University of Alabama at Birmingham

Status: Completed

Conditions: Parkinson's Disease

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT01860118

X121207003

1U18NS082132 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This proposal seeks to 1) determine whether there are biomarkers associated with Parkinson's disease (PD) susceptibility and/or progression in exosome-proteomes derived from PD patients versus controls, and 2) to determine if LRRK2 expression and/or phosphorylation are significantly lowered in the exosomes of individuals treated with the potent LRRK2 kinase inhibitor sunitinib (a multi-kinase inhibitor compound), to establish an assay for on-target effects for future LRRK2 inhibitor clinical trials.

Enrollment: 601 patients

Sex: All

Ages: 21+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Parkinson's disease inclusion criteria:

Inclusion criteria will be based on UK Brain Bank criteria for the clinical diagnosis of PD. These require 1) the presence of bradykinesia and either rest tremor or rigidity; 2) asymmetric onset; 3) progressive motor symptoms 4) age at onset 21-99 years.

Control inclusion criteria: ages of between 21-99 years, a lack of PD in first-degree blood relatives, and a lack of positive responses on more than 3 items on the PD Screening Questionnaire.

Exclusion criteria

For all subjects:

include atypical features indicative of a Parkinson-Plus disorder (Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA), Corticobasal Degeneration (CBD)) including cerebellar signs, supranuclear gaze palsy, apraxia and other cortical signs, or prominent autonomic failure, neuroleptic treatment at time of onset of parkinsonism, active treatment with a neuroleptic at time of study entry, History of repeated strokes with stepwise progression of parkinsonism, history of repeated head injury, history of definite encephalitis, prominent gait imbalance early in the course (< 5 years), dementia, known severe anemia (hematocrit <30), history of kidney disease and/or current or past glomerular filtration rate (GFR) <60 possibly indicative of kidney disease, or a serious comorbidity that may interfere with participation in the study.

Trial design

601 participants in 2 patient groups

Parkinson's Disease

Description:

1) the presence of bradykinesia and either rest tremor or rigidity; 2) asymmetric onset; 3) progressive motor symptoms 4) age at onset 21-99 years.

Healthy Control

Description:

Healthy controls between ages of 21-99 years and a lack of PD in first-degree blood relatives