Parkinson’s disease (PD) is a common neurodegenerative disease that leads to progressive motor impairment as well as autonomic and cognitive disturbances. The cause of most of the forms of PD is not yet understood, which hampers the development of therapeutic strategies. Moreover, the disease is generally detected when a large proportion of neurons have already degenerated, which reduces the utility of potential neuroprotective therapies. In some forms, however, genetic mutations are associated with increased risk of the disease and mutation carriers can be identified. In these forms the pathological processes can be studied in the very early (”pre-Symptoms & Side Effects”) phase to establish biomarkers for the disease as well as in the phase in which motor symptoms are apparent to establish progression markers. These findings can be used for a better understanding of other non-genetic forms. LRRK2 mutations are a fairly common cause of the rare forms of inherited PD and patients with this type of mutation share many clinical and pathologic characteristics with the common sporadic form of the disease.
We aim to evaluate biomarkers (parameters of the blood, CSF, urine or from cultivated skin cells) as well as clinical and imaging characteristics in LRRK2 patients and pre-Symptoms & Side Effects mutation carriers in comparison to sporadic PD and healthy controls to assess potential risk and progression markers for the disease.
This is a five year prospective, observational study to assess potential biomarkers as well as clinical and imaging characteristics for disease status and progression in the following cohorts: Symptoms & Side Effects LRRK2 mutation carriers affected by PD, sporadic PD patients, aSymptoms & Side Effects LRRK2 mutation carriers and age-matched healthy controls. The subjects attend one clinical visit per year and undergo the following assessments: a comprehensive clinical examination to evaluate potential motor impairment and non-motor dysfunction (dementia, depression, olfactory dysfunction, constipation). We further perform transcranial sonography (TCS) and magnetic resonance imaging (MRI) to detect structural changes of the brain morphology. Body fluids (blood, cerebrospinal fluid, urine) are collected to identify biomarkers that are related to a possible risk or disease status and may help to indicate the neurodegenerative process not only in affected patients but even in a pre-clinical stage of disease.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The collection of clinical and imaging data and analyses of biological fluids may allow the identification of markers that could be used to diagnose PD much earlier than is currently possible (i.e. in the pre-Symptoms & Side Effects phase) and other markers that help to understand individual progression. Furthermore, these data will contribute to the understanding of relevant pathways underlying this neurodegenerative disorder. It is hoped that findings will contribute to a basis for novel targets for causative or even preventive treatments.
We hypothesize that by longitudinal clinical and neuroimaging examination and collection of biomaterials of patients with and without LRRK2 mutations in different stages of the disease we will be able to identify markers related to disease status, to the neurodegenerative process itself (even in a pre-Symptoms & Side Effects stage) and/or to specific clinical or imaging features. Furthermore, such studies will lay the basis for revealing signaling pathways which are critically regulated by LRRK2 as well as determining the role of LRRK2 in the development of PD.