PLASMA CELL-FREE RNA AS NON-INVASIVE BIOMARKER FOR NEURODEGENERATION - PROJECT SUMMARY / ABSTRACT ALZHEIMER…

Assistance award details

Assistance award identifier

ASST_NON_R00AG062723_075

FAIN

R00AG062723

Recipient

WASHINGTON UNIVERSITY, THE

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$727,992

Period

Feb 1, 2020 – Mar 31, 2025

Fiscal year

2022

Place of performance state

MO

Source file

FY2022_All_Assistance_Full_20261006.zip

Description

PLASMA CELL-FREE RNA AS NON-INVASIVE BIOMARKER FOR NEURODEGENERATION - PROJECT SUMMARY / ABSTRACT ALZHEIMER DISEASE (AD) IS THE MOST COMMON NEURODEGENERATIVE DISORDER. PATHOLOGICAL CHANGES IN THE BRAIN CAN BE OBSERVED AT LEAST 15 YEARS BEFORE CLINICAL SYMPTOMS (PRECLINICAL STAGE). AN EARLY AND ACCURATE DIAGNOSIS TOOL COULD SAVE $7.9 TRILLION IN MEDICAL AND CARE COSTS. MOREOVER, AN EFFECTIVE THERAPEUTIC STRATEGY COULD IMPROVE THE CLINICAL OUTCOME IF DELIVERED EARLY. THERE IS A CLEAR NEED TO DEVELOP COST-EFFECTIVE AND NON-INVASIVE BIOMARKERS FOR AD THAT CAN BE USED TO IDENTIFY INDIVIDUALS BEFORE SYMPTOMS EMERGE AND PATIENTS AT EARLY-SYMPTOMATIC STAGES OF DISEASE. THESE NOVEL BIOMARKERS COULD BE ALSO LEVERAGED TO MONITOR DISEASE PROGRESSION AND RESPONSES TO THERAPIES. CELL-FREE NUCLEIC ACIDS DIAGNOSTIC TESTS HAVE REVOLUTIONIZED PRENATAL SCREENING, AND CANCER RESEARCH, DIAGNOSIS AND TREATMENT. FURTHERMORE, SPECIFIC TRANSCRIPTS ASCERTAINED FROM CELL-FREE RNA HAVE BEEN EVALUATED AS BIOMARKERS FOR AD, BUT SO FAR, NO HIGH THROUGHPUT APPROACH HAS BEEN ATTEMPTED. THE GOAL OF THIS PROPOSAL IS TO USE HIGH THROUGHPUT SEQUENCING OF CELL-FREE NUCLEIC ACIDS FROM PLASMA TO CONSTRUCT A PREDICTION MODEL FOR NEURODEGENERATIVE DISEASES. I HYPOTHESIZE THAT THERE ARE DETECTABLE CHANGES IN PLASMA CELL-FREE NUCLEIC ACIDS THAT ARE RELATED TO AD. DURING THE K99 PHASE, I AIM TO PREDICT ACCURATELY AD CASES USING CELL-FREE NUCLEIC ACID AND BIOINFORMATICS TOOLS, INCLUDING MACHINE LEARNING. BRIEFLY, I WILL SEQUENCE CELL-FREE RNA PRESENT IN LONGITUDINAL SAMPLES OF PLASMA FROM AD CASES AND CONTROLS, THEN BUILD A PREDICTIVE MODEL. I WILL REPLICATE THIS MODEL IN AN INDEPENDENT DATASET OF PRECLINICAL SAMPLES. I WILL INCLUDE SAMPLES FROM MUTATION CARRIERS AND NON-EUROPEAN ANCESTRY TO VALIDATE THE MODEL. I WILL ALSO DETERMINE IF THE MODEL CAN PREDICT OTHER NEURODEGENERATIVE DISEASES OR IF IT IS SPECIFIC TO AD BY QUANTIFYING PLASMA TRANSCRIPTS FROM PATIENTS WITH OTHER NEURODEGENERATIVE DISEASES. MY PRELIM