Plasma Cell-Free RNA as Noninvasive Biomarker for Parkinson s Disease
Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. There is no cure available, and the tools to diagnose and follow-up the disease are limited. The commonalities across neurodegenerative diseases makes very difficult the differential diagnosis between Alzheimer’s disease (AD), PD, Lewy body dementia among many others. In this proposal, we aim to create a tool that allows to differentially diagnose PD using an innovative approached. Prenatal testing was revolutionized by the use of cell-free nucleic acids. We propose to apply the same principle to create a tool to diagnose and follow-up PD. We have successfully developed a preliminary tool for AD using cell-free plasma RNA sequencing and state-of-the-art bioinformatics techniques with good results in independent populations. This means that we can identify individuals that will progress to dementia. We think this technique can be also useful to diagnose PD. We hypothesize that there are detectable changes in the plasma nucleic acid composition due to PD pathogenesis, even in early stages. We will use bioinformatics tools to construct a predictive model for PD. First, we will create the tool to predict PD in three steps: (A) Select the best pieces of information from the cell-free nucleic acids to model the tool using bioinformatics. We will use 200 plasma samples from 50 PD individuals at three time-points – early pre-clinical (5-10 years before symptoms), pre-clinical (2-5 years before symptoms) and symptomatic (5-8 years after diagnostic) and 50 controls. (B) We will use the information obtained from A and see if it also predicts PD in another population. We will also use a molecular technique that can be easily translated into a clinical lab tool. This will be the first step toward commercialization. Finally, it is known that there are many commonalities across neurodegenerative disease. In consequence, the last step will be (C): Test that the tool is not predicting other neurodegenerative disease. We will apply evaluate the performance of our diagnostic tool in 80 cases of other neurodegenerative diseases (AD, Lewy body dementia, progressive supranuclear palsy, amyotrophic lateral sclerosis and frontotemporal dementia) and 40 controls. We expect the predictive model to be specific for PD; however, some overlap is expected. To learn the biological meaning of this diagnostic tool, we will mix the data of PD with the one from AD (available in our lab). This will allow us to describe biological differences and commonalities across the two most common neurodegenerative diseases, the description of biological mechanisms, differences in the timeline of the disease and the improvement of the differential diagnosis. If successful, this method could improve the cost-effectiveness of the currently available tools to diagnose and monitor PD, and provide a scalable blood-based early diagnostic screening tool. We have included a step to scale the diagnostic tool and reduce its price; however, many other tests and regulatory steps are needed before final commercialization. Dr. Ibanez’s research interest is focused on using genetics to improve the management of individuals that suffer from neurodegenerative diseases, especially the early management by using state-of-the-art technologies and bioinformatics. She want to apply this interest to early diagnostic that can easily be used in clinical settings to improve the management and quality of life of patients. In the last year and a half, Dr. Ibanez efforts have been focused on creating predictive models for AD using different approaches. Even though this model is on preliminary stages, she has proven that she can successfully create predictive models using this innovative approach and the unique sample repository to which she has access through her mentor. This proposal will allow her to leverage the data generated biologically, which could add some biological understanding to the biol
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010849
Entities
People
- Laura Ibanez
Organizations
- United States Army
- Washington University in St. Louis