Study Rationale: Families, caregivers, and individuals living with Parkinson’s disease are in need of new biomarkers and effective therapies. To date, most of the studies have focused on DNA and proteins, ignoring important regulatory molecules, the transcripts. We propose to study these ignored molecules to find new therapies using a computational approach.
Hypothesis: We hypothesize that there are transcriptomic changes related to PD that can be used to nominate novel therapeutic targets.
Study Design: This proposal has a sequential scientific plan composed of one aim in which we will process the brain transcriptome from PD and controls to identify differentially expressed transcripts, integrate the different transcript types and build networks, map out the genomic regulatory regions to increase the sample size by inferring brain transcriptomic levels in more than 3,000 individuals to identify additional transcripts. All the transcripts identified, especially those that are estimated to be causally associated to PD, will be screened against publicly available drug databases for potential repurposing.
Impact on Diagnosis/Treatment of Parkinson’s disease: This proposal will characterize the PD transcriptome for the first time providing better understanding of the regulatory pathways associated with PD and propose novel therapeutic targets.
Next Steps for Development: This study is the first of its kind. All proposed therapeutical targets will need to be validated, and drugs developed and tested via the appropriate clinical trial design.