R43AG080844
Project Grant
Overview
Grant Description
Diagnostic Aptamer Reagents to Develop Multi-Analyte Blood Test for Pre-Clinical, Mild and Moderate Alzheimer's Disease - Diagnostic Aptamer Reagents to Develop Multi-Analyte Blood Test for Pre-Clinical, Mild and Moderate Alzheimer’s Disease
Aptus Biosciences, LLC Bharat Gawande Summary
Today, 6.2 million Americans are living with Alzheimer’s Disease (AD), resulting in $355 billion in annual medical care costs. As the US population over age 65 grows, the number of Americans living with AD is expected to increase to 12.7 million by 2050.
AD is a slow progressing disease, and it may take up to 20 years before symptoms are recognizable. While new treatments are emerging that may help to control or modify the disease, early detection using a simple blood test is critical to individuals with AD.
Importantly, recent studies have shown promising results with blood-based biomarkers that are specific for AD. However, there is clearly a lack of high affinity reagents that can bind to these biomarkers and be used to develop sensitive and easily accessible blood tests.
Aptus Biosciences will use modified aptamer selection technology to create highly sensitive and specific reagents that detect blood biomarkers of AD which cause neurofibrillary tangles (NFTs), a hallmark of AD. We will deliver aptamer reagents developed from an improvised in vitro selection method using hydrophobic modified nucleotides that can bind to tau protein, and multiple isoforms of phosphorylated tau (P-Tau) protein with pico-molar affinity.
Each targeted selection will generate aptamers that bind to various epitopes on specific P-Tau targets with picomolar affinity and that will be used to develop a simple bead-based aptamer sandwich assay. In this assay, one aptamer will capture P-Tau biomarker and another aptamer will result in a signal generation to measure the plasma concentrations of these analytes.
Our modified aptamer reagents are potentially better than unmodified aptamers and large antibody-based reagents, which are not as sensitive or specific because of their large size, low affinity, and cross-reactivity in multi-analyte assays. Specifically, we will use selections to create modified aptamers that bind to specific validated phosphorylated isoforms of tau.
In addition, we will develop a simple bead-based multi-analyte aptamer sandwich assay to measure P-Tau isoforms in plasma samples obtained from cerebrospinal fluid (CSF) ASS42 positive, AD-confirmed individuals and compare them with plasma samples obtained from cognitively normal, ASS42 negative individuals without AD.
If this Phase I grant is successful, in Phase II, we will optimize aptamer reagents to improve the sensitivity and specificity of the assay, scale-up aptamer reagent production, develop a cloud-based algorithm using a training sample set, and validate the assay using test samples to correctly identify early AD in a large cohort.
The multi-analyte aptamer-based assay will make it far superior to existing qualitative, invasive, and expensive diagnostic tests. If successful, this simple blood test will enhance the lives of millions of Americans who are at high risk of developing AD due to the ability of the test for early detection, thus resulting in early treatment interventions and decreasing the huge economic burden to the healthcare system.
Aptus Biosciences, LLC Bharat Gawande Summary
Today, 6.2 million Americans are living with Alzheimer’s Disease (AD), resulting in $355 billion in annual medical care costs. As the US population over age 65 grows, the number of Americans living with AD is expected to increase to 12.7 million by 2050.
AD is a slow progressing disease, and it may take up to 20 years before symptoms are recognizable. While new treatments are emerging that may help to control or modify the disease, early detection using a simple blood test is critical to individuals with AD.
Importantly, recent studies have shown promising results with blood-based biomarkers that are specific for AD. However, there is clearly a lack of high affinity reagents that can bind to these biomarkers and be used to develop sensitive and easily accessible blood tests.
Aptus Biosciences will use modified aptamer selection technology to create highly sensitive and specific reagents that detect blood biomarkers of AD which cause neurofibrillary tangles (NFTs), a hallmark of AD. We will deliver aptamer reagents developed from an improvised in vitro selection method using hydrophobic modified nucleotides that can bind to tau protein, and multiple isoforms of phosphorylated tau (P-Tau) protein with pico-molar affinity.
Each targeted selection will generate aptamers that bind to various epitopes on specific P-Tau targets with picomolar affinity and that will be used to develop a simple bead-based aptamer sandwich assay. In this assay, one aptamer will capture P-Tau biomarker and another aptamer will result in a signal generation to measure the plasma concentrations of these analytes.
Our modified aptamer reagents are potentially better than unmodified aptamers and large antibody-based reagents, which are not as sensitive or specific because of their large size, low affinity, and cross-reactivity in multi-analyte assays. Specifically, we will use selections to create modified aptamers that bind to specific validated phosphorylated isoforms of tau.
In addition, we will develop a simple bead-based multi-analyte aptamer sandwich assay to measure P-Tau isoforms in plasma samples obtained from cerebrospinal fluid (CSF) ASS42 positive, AD-confirmed individuals and compare them with plasma samples obtained from cognitively normal, ASS42 negative individuals without AD.
If this Phase I grant is successful, in Phase II, we will optimize aptamer reagents to improve the sensitivity and specificity of the assay, scale-up aptamer reagent production, develop a cloud-based algorithm using a training sample set, and validate the assay using test samples to correctly identify early AD in a large cohort.
The multi-analyte aptamer-based assay will make it far superior to existing qualitative, invasive, and expensive diagnostic tests. If successful, this simple blood test will enhance the lives of millions of Americans who are at high risk of developing AD due to the ability of the test for early detection, thus resulting in early treatment interventions and decreasing the huge economic burden to the healthcare system.
Awardee
Funding Goals
TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Florida
United States
Geographic Scope
State-Wide
Related Opportunity
Analysis Notes
Amendment Since initial award the End Date has been extended from 01/31/24 to 01/31/25.
Aptus Biosciences was awarded
Project Grant R43AG080844
worth $445,554
from National Institute on Aging in February 2023 with work to be completed primarily in Florida United States.
The grant
has a duration of 2 years and
was awarded through assistance program 93.866 Aging Research.
The Project Grant was awarded through grant opportunity Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R43/R44 Clinical Trial Optional).
SBIR Details
Research Type
SBIR Phase I
Title
Diagnostic aptamer reagents to develop multi-analyte blood test for pre-clinical, mild and moderate Alzheimer's disease
Abstract
Diagnostic aptamer reagents to develop multi-analyte blood test for pre-clinical, mild andmoderate Alzheimer’s disease Aptus Biosciences, LLCBharat Gawande SummaryToday, 6.2 million Americans are living with Alzheimer’s disease (AD), resulting in $355 billion in annual medical care costs. As the US population over age 65 grows, the number of Americans living with AD is expected to increase to 12.7 million by 2050. AD is a slow progressing disease, and it may take up to 20 years before symptoms are recognizable. While new treatments are emerging, that may help to control or modify the disease, early detection using a simple blood test is critical to individuals with AD. Importantly, recent studies have shown promising results with blood-based biomarkers that are specific for AD. However, there is clearly a lack of high affinity reagents that can bind to these biomarkers and be used to develop sensitive and easily accessible blood tests.Aptus Biosciences will use modified aptamer selection technology, to create highly sensitive and specific reagents that detect blood biomarkers of AD which cause neurofibrillary tangles (NFTs), a hallmark of AD. We will deliver aptamer reagents developed from an improvised In Vitro selection method using hydrophobic modified nucleotides that can bind to tau protein, and multiple isoforms of phosphorylated tau (p-tau) protein with pico-molar affinity. Each targeted selection will generate aptamers that bind to various epitopes on specific p-tau targets with picomolar affinity and that will be used to develop a simple bead-based aptamer sandwich assay in which one aptamer will capture p-tau biomarker and other aptamer will result in a signal generation to measure the plasma concentrations of these analytes. Our modified aptamer reagents are potentially better than unmodified aptamers and large antibody-based reagents, which are not as sensitive or specific because of their large size, low affinity, and cross-reactivity in multi-analyte assays. Specifically, we will use selections to create modified aptamers that bind to specific validated phosphorylated isoforms of tau. In addition, we will develop a simple bead-based multi-analyte aptamer sandwich assay to measure p-tau isoforms in plasma samples obtained from cerebrospinal fluid (CSF) Aβ42 positive, AD-confirmed individuals and compare them with plasma samples obtained from cognitively normal, Aβ42 negative individuals without AD.If this Phase I grant is successful, in Phase II, we will optimize aptamer reagents to improve the sensitivity and specificity of the assay, scale-up aptamer reagent production, develop a cloud-based algorithm using a training sample set, and validate the assay using test samples to correctly identify early AD in a large cohort. The multi- analyte aptamer-based assay will make it far superior to existing qualitative, invasive, and expensive diagnostic tests. If successful, this simple blood test will enhance the lives of millions of Americans who are at high risk of developing AD due to the ability of the test for early detection, thus resulting in early treatment interventions and decreasing the huge economic burden to the healthcare system.
Topic Code
NIA
Solicitation Number
PAS19-316
Status
(Complete)
Last Modified 6/5/25
Period of Performance
2/1/23
Start Date
1/31/25
End Date
Funding Split
$445.6K
Federal Obligation
$0.0
Non-Federal Obligation
$445.6K
Total Obligated
Activity Timeline
Transaction History
Modifications to R43AG080844
Additional Detail
Award ID FAIN
R43AG080844
SAI Number
R43AG080844-3945231048
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Small Business
Awarding Office
75NN00 NIH National Insitute on Aging
Funding Office
75NN00 NIH National Insitute on Aging
Awardee UEI
P69KB94KHH28
Awardee CAGE
98HN7
Performance District
FL-90
Senators
Marco Rubio
Rick Scott
Rick Scott
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Institute on Aging, National Institutes of Health, Health and Human Services (075-0843) | Health research and training | Grants, subsidies, and contributions (41.0) | $445,554 | 100% |
Modified: 6/5/25