The Epidemiology of Parkinson's Disease in Croatia and the Influence of Genetic Factors and Microbiota on the Progression and Treatment Outcomes of the Disease (GiOPARK)

Summary

Parkinson's disease (PD) is the second most common neurodegenerative disease, which affects 2-3% of the general population above 65 years. There are significant differences in incidence depending on geographical location, race, and ethnicity. The exact cause of the disease is still unknown, but the role of genetic and environmental factors has already been established. Certain genetic forms of the disease make up for a small percentage, so it is thought that environmental factors have a more significant impact on the development of the disease. The incidence of PD is higher in people exposed to significant quantities of pesticides and traumatic brain injury, while there is a smaller incidence in smokers and people consuming more significant quantities of caffeine. The project will finish in four years, with the first 20 months dedicated to the first phase (genetic-epidemiological research), and the entirety of the 48 months for the second phase of the project (prospective clinical research).

The main goal of the first phase of the project is to determine which genetic mutations are the ones most represented in the Croatian population afflicted with the familial form of PD. In the second phase the main goal is to determine the influence of genetic factors and microbiological factors on the disease's progression as well as on the treatment outcomes. Specific goals of this part of the project are to determine how many patients in the general population of PD patients present with a genetic disorder and which genes have a role in that disorder, as well as determine the composition of intestinal and oral microbiota both in the patient test group and the healthy control group. Furthermore, specific goals are to evaluate the effects of standard PD treatment on the composition of microbiota, neurodegeneration progression and the activity of neuroinflammation in the central nervous system (CNS) and to examine whether there is a link between the physiological and the pathophysiological function of microbiota, using markers of disease progression and glial activity. Last specific goal is to analyze potential pathological conformation protein forms that could be used as a biomarker in early stages of the disease and a biomarker of disease progression.

The first phase of the study will provide the first epidemiologic data on the familial form of PD, as well as the mutations most represented in patients with PD in Croatia. Additionally, the prospective clinical study will contribute to enlightening the intertwined effects of genetic and environmental factors in the emergence and progression of the disease, as well as their effect on treatment outcome. Intestinal and oral microbiota composition analysis will determine whether there is a difference between PD and the healthy population while using the short-chain fatty acid profile will determine the metabolic differences between the two groups. Analyzing the markers of CNS homeostasis, inflammation, and neuroglial function will determine the progression of the disease and also correlate them to genetic factors as well as the microbiota function and composition. Analyzing the pathological conformation forms of alpha-synuclein could lead to the discovery of novel biomarkers in the early stages of the disease, as well as to follow the progression of the disease

Conditions

• Parkinson Disease
• Genetic Disease
• Microbiota
• Neuro-Degenerative Disease
• Neuroinflammatory Response

Interventions

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Whole-exome sequencing

Whole-exome sequencing with the focus on Parkinson's disease loci.

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Microbiota sequencing

Next generation sequencing of microbiota from stool and saliva samples.

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Magnetic resonance imaging

Magnetic resonance imaging of the brain focused on detection of free water in Substantia Nigra using a novel protocol.

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Transcranial ultrasound and Electroencephalography

Transcranial ultrasound of Substantia Nigra, as well as high resolution EEG.

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ELISA (Enzyme-Linked Immunosorbent Assay)

ELISA (Enzyme-Linked Immunosorbent Assay) will be used to assess the inflammatory state, glial functions, and disease progression will also be determined through specific markers in the participant's serum and plasma samples

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Fluorescent correlation spectroscopy (FCS)

Fluorescent correlation spectroscopy (FCS), more specifically, ThT fluctuating intensity fluorescent analysis (FIFA) will be used to determine the existence of pathological conformation protein forms and their relation to the disease's grade and therapy.

Sponsors & Collaborators

• University Medical Centre Ljubljana

  collaborator OTHER

• Croatian Science Foundation

  collaborator OTHER_GOV

• Karolinska Institutet

  collaborator OTHER

• Clinical Hospital Center Rijeka

  lead OTHER

Principal Investigators

• Vladimira Vuletic · Clinical Hospital Center Rijeka

Eligibility

Min Age

18 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-05-01

Primary Completion

2023-08-01

Completion

2024-02-01

Countries

• Croatia

Study Locations