Funded Studies
Objective/Rationale:
LRRK2 mutations constitute one of the most common genetic risk factors for PD. The prospective follow-up of PD patients and aSymptoms & Side Effects carriers of LRRK2 mutations will provide a unique opportunity to capture the neurodegenerative process before its clinical onset and to identify markers that reflect its progression. The main objective of this proposal is to increase the follow up time of an existing cohort of PD patients and aSymptoms & Side Effects subjects with LRRK2 mutations, in order to prospectively validate clinical, biological or imaging biomarkers.
Project Description:
We will take advantage of our existing transversal (n = 164) and prospective (n = 45) cohort of PD patients and aSymptoms & Side Effects subjects with LRRK2 mutations. Subjects will be followed with state of the art of clinical, brain imaging (MRI and PET) and biological assessment for up to 3 years, in order to identify surrogate markers of neurodegeneration for preventive therapeutic strategies in PD.
Specific aims:
(i) To describe the LRRK2 phenotype, frequency and mutation spectrum by a systematic LRRK2 genetic screening in new PD patients;
(ii) To identify clinical and brain imaging differences between LRRK2 patients, aSymptoms & Side Effects LRRK2 mutation carriers and healthy controls;
(iii) To identify gene expression differences in blood cells between aSymptoms & Side Effects LRRK2 patients, aSymptoms & Side Effects LRRK2 mutation carriers and healthy controls;
(iv) To collect fibroblasts for future establishment of induced pluripotent stem cells (iPS);
(v) To define the anatomo-pathological spectrum of LRRK2 mutation by genotyping post-mortem brain samples from PD patients already collected at the Salpêtrière brain bank.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
No treatment can as yet effectively modify the course of the disease itself, partly because of the incompressible delay between the onset of the pathological process and therapeutic intervention. There is a need to identify surrogate markers that predict PD onset and allow for the monitoring of the neurodegenerative process over time. The final aim of this project is to identify predictive markers of PD onset, in order to develop preventive therapeutic strategies. Sharing the clinical and technical data within MJFF’s LRRK2 consortium will greatly increase the power of statistical and correlation analyses.
Anticipated Outcome:
In addition to the description of the clinical and genetic spectrum of PD patients with LRRK2 mutation, we aim at identifying clinical, brain imaging and/or biological markers correlated with PD onset and disease progression. These surrogate markers will be crucial for future clinical trials testing for new neuroprotective therapies in PD. Sharing the clinical and technical data within MJFF LRRK2 consortium will greatly increase the power of statistical and correlation analyses.