The Leucine-Rich Repeat Kinase 2 (LRRK2) is implicated in autosomal dominant Parkinson's disease (PKD). An inhibitor for the leucine-rich repeat kinase 2 (LRRK2) is in pre-clinical development for potential use in treating Parkinson's disease. Patients with PKD have cognitive impairments which develop alongside the typical motor symptoms but a full characterisation of the neurocognitive phenotype of PKD patients with LRRK2 mutation is currently lacking. This observational study conducted on a single visit will assess the phenotypic neurocognitive abnormalities of PKD patients with the LRRK2 mutation with the aim of identifying potential PD endpoints related to the LRRK2 mutation for future Phase I or II clinical trials of LRRK2 inhibitors.

NCT01424475

Conditions

1. Parkinson Disease

Interventions

1. Genetic: Healthy
2. Genetic: PKD Patients

MeSH:Parkinson Disease

- Confirmed ascertainment as having the G2019S mutation in the LRRK2 gene. --- G2019S ---

The clinical and pathological similarities between LRRK2 related parkinsonism and idiopathic Parkinson's disease (PD) indicate that monogenetic LRRK2 parkinsonism may be a paradigm for the development of Lewy bodies disease, and a careful look at discrepancies between these two conditions may provide insight into the pathogenesis of PD. The early involvement of the enteric nervous system (ENS) during PD led to theories that an as yet unidentified external agent entering the ENS causes PD . If lesions of the ENS are found in patients who present with a genetic form of parkinsonism would go against this notion, and thus provide insight to the pathophysiology of the disease.

NCT01618383

Conditions

1. Parkinson's Disease

Interventions

1. Other: colonoscopy or rectosigmoidoscopy

MeSH:Parkinson Disease

Inclusion Criteria: - Patients aged 30-80, both genders - Parkinson's disease patients - Parkinson's disease patients with G2019S mutations - Controls: patient at risk of colic cancer for whom a coloscopy is required Inclusion Criteria: - Patients aged 30-80, both genders - Parkinson's disease patients - Parkinson's disease patients with G2019S mutations - Controls: patient at risk of colic cancer for whom a coloscopy is required Parkinson's Disease Parkinson Disease null --- G2019S ---

Inclusion Criteria: - Patients aged 30-80, both genders - Parkinson's disease patients - Parkinson's disease patients with G2019S mutations - Controls: patient at risk of colic cancer for whom a coloscopy is required Inclusion Criteria: - Patients aged 30-80, both genders - Parkinson's disease patients - Parkinson's disease patients with G2019S mutations - Controls: patient at risk of colic cancer for whom a coloscopy is required Parkinson's Disease Parkinson Disease null --- G2019S --- --- G2019S ---

This is a longitudinal study in patients with Parkinson's Disease (PD) carriers of a genetic mutation - substitution of gly with ser in position 2019 (G2019S) in the leucine-rich repeat kinase 2 (LRRK2) gene. The purpose of this study is to explore the association between genetic mutations in the known genes and their influence on disease manifestation over few years of follow up

NCT01730599

Conditions

1. Parkinson's Disease

Interventions

1. Other: neurological exam

MeSH:Parkinson Disease

A Longitudinal 5 Years Follow up Study in Parkinson's Disease (PD) Patients Carriers of the LRRK2 Gene G2019S Mutation. --- G2019S ---

A Longitudinal Study in Parkinson's Disease (PD) Patients This is a longitudinal study in patients with Parkinson's Disease (PD) carriers of a genetic mutation - substitution of gly with ser in position 2019 (G2019S) in the leucine-rich repeat kinase 2 (LRRK2) gene. --- G2019S ---

The primary objective of this protocol is to access the utility of 18F-DTBZ PET imaging as an in vivo biomarker to monitor neurodegeneration of both PD mouse models and PD patients. Secondary, the investigators will analyze progression rate of genetic-proving PARK8 and PARK6 patients who have homogeneous phenotype and genotype by 18F-DTBZ PET imaging.

NCT01759888

Conditions

1. Parkinson's Disease

Interventions

1. Drug: 18F-DTBZ

MeSH:Parkinson Disease Parkinsonian Disorders Nerve Degeneration

HPO:Neurodegeneration Parkinsonism

Patients didn't have other mutations that may contribute to the parkinsonism, such as LRRK2 G2019S, LRRK2 R1628P, PARK2, PARK6, and SCA2. --- G2019S ---

Primary Objectives: - Part 1: To determine the safety and tolerability of GZ/SAR402671 administered orally, as compared to placebo in patients with early-stage Parkinson's disease (PD) carrying a GBA mutation or other pre-specified variants. - Part 2: To determine the efficacy of GZ/SAR402671 administered orally daily, as compared to placebo in patients with early-stage Parkinson's disease carrying a GBA mutation or other pre-specified variants. Secondary Objectives: Part 1: - To assess the pharmacokinetic (PK) profile of oral dosing of GZ/SAR402671 in plasma when administered in early-stage Parkinson's disease patients carrying a GBA mutation. - To assess the exposure of GZ/SAR402671 in cerebrospinal fluid (CSF) when administered in early-stage Parkinson's disease patients carrying a GBA mutation. Part 2: - To demonstrate overall safety and tolerability of GZ/SAR402671 administered orally in early-stage Parkinson's disease patients carrying a GBA mutation as compared to placebo. - To assess the pharmacodynamic response to daily oral dosing of GZ/SAR402671 in plasma and CSF as measured by glucosylceramide (GL-1) when administered in early-stage Parkinson's disease patients carrying a GBA mutation.

NCT02906020

Conditions

1. Parkinson's Disease

Interventions

1. Drug: GZ/SAR402671
2. Drug: Placebo

MeSH:Parkinson Disease

- Patients carrying mutations in genes other than GBA that have been associated with an increased risk for PD, specifically LRKK2 (G2019S). --- G2019S ---

The goals of this study are 1. To compare the functional effects of the LRRK2 G2385R variant among carriers with and without Parkinson's disease (PD) and non-carriers with and without PD 2. To investigate the relationship between functional effects of the LRRK2 G2385R variant and PD associated phenotype 3. To investigate the biomarkers associated with PD conversion in the LRRK2 G2385R variant carriers 4. To compare the immune-related differences between PD patients/unaffected individuals with and without the LRRK2 G2385R mutation, and to investigate the effects of immune dysfunction on the clinical expression of PD

NCT04349865

Conditions

1. Parkinson Disease

MeSH:Parkinson Disease

While the LRRK2 G2019S mutation is the most common mutation present in Caucasians and certain ethic groups, the G2385R variant has been identified as a risk factor for sporadic PD in the Asian population (Chinese Han, Japanese and Korean). --- G2019S ---

In fact, in these populations, the occurrence of this mutation is thought to be higher than (up to 4% of PD patients) the occurrence of the G2019S mutation in the Caucasian population. --- G2019S ---

In contrast to G2019S, this variant has not been fully characterized. --- G2019S ---

The goal of this study is to identify reliable markers of LRRK2 activity in human CSF.

NCT04603326

Conditions

1. Parkinson Disease

Interventions

1. Procedure: Lumbar Puncture

MeSH:Parkinson Disease

Evaluate each assay performance for ability to detect LRRK2, its activity and/or the detection and activity of the pathways it impacts using a variety of different approaches (quantitative western blot, immunoassays and LC-MS).. Non-manifesting LRRK2 mutation carriers Inclusion: Patients must have confirmed LRRK2 G2019S mutation Age 30 years or older at date of informed consent. --- G2019S ---

Diagnosis of dementia LRRK2 Parkinson Disease (PD) Participants: Inclusion: Patients must have confirmed LRRK2 G2019S mutation Patients must meet the MDS criteria for Parkinson's disease Disease duration: any Age 30 years or older at time of PD diagnosis. --- G2019S ---

Exclusion: Inability to provide informed consent Known GBA mutation carrier In the absence of prior genetic testing for LRRK2 G2019S mutations: Family history of Parkinson's disease is an exclusion criterion. --- G2019S ---

If genetic testing for LRRK2 G2019S has been performed and is negative, individuals with a family history of PD may be enrolled. --- G2019S ---

In the absence of prior genetic testing for LRRK2 G2019S mutations: Family history of Parkinson's disease is an exclusion criterion. --- G2019S ---

If genetic testing for LRRK2 G2019S mutations has been performed and is negative, individuals with a family history of PD may be enrolled. --- G2019S ---

Diagnosis of dementia Non-manifesting LRRK2 mutation carriers Inclusion: Patients must have confirmed LRRK2 G2019S mutation Age 30 years or older at date of informed consent. --- G2019S ---