SB1AG050454
Project Grant
Overview
Grant Description
Use of Novel Fluorescent Tracers to Develop a Comprehensive Retinal Biomarker Database that Maps the Heterogeneity of Alzheimer's Pathogenesis - Project Summary
Alzheimer’s disease (AD), the most common form of dementia, has traditionally been defined by the accumulation of amyloid beta (ASS) in neuritic plaques and hyperphosphorylated tau in neurofibrillary tangles. However, recent evidence indicates that AD is better viewed as a continuum of disease with a broader degree of mechanistic and pathological heterogeneity.
For example, ~15% of AD patients are negative for ASS and most AD patients have “mixed pathology”, with large subsets exhibiting accumulation of additional neurodegenerative biomarkers such as a-synuclein (A-SYN) and the TDP-43. Hippocampal and amygdalar deposits of TDP-43 have recently been characterized as defining a disease state that overlaps heavily with AD: limbic-predominant, age-related TDP-43 encephalopathy (LATE).
At present, AD diagnosis relies on clinical evaluation of symptoms and PET imaging of ASS and tau load. However, this is costly, involves exposure to radiation, and does not have the ability to detect broader dimensions of AD heterogeneity, such as the presence of pathological A-SYN and TDP-43 deposits that define large subsets of the AD continuum.
There is an unmet medical need for an antemortem diagnostic that can reliably identify mechanistic heterogeneity in individual AD patients, ideally one that can detect multiple disease-related biomarkers simultaneously and non-invasively in CNS tissue.
Amydis is leveraging the retina as a “window to the brain” to address this unmet need by developing an ocular contrast agent – i.e. a “retinal tracer – that can be used to fluorescently label A-SYN, TDP-43, and ASS in patients suspected of having AD. The retinal tracer, AMDX-2011P, currently in human clinical trials, has these remarkable capabilities and is designed to have fluorescent properties amenable for use with standard retinal imaging equipment found in the eye care office, making this technology widely accessible.
In this proposal, Amydis will take the first clinical steps towards developing transformative new diagnostic technology in AD focusing on the biomarker ASS in AD patient retinas. The specific aims of the project are: (1) to develop a lyophilized product of AMDX-2011P for I.V. delivery; (2) to complete a phase 1B clinical trial of AMDX-2011P in patients with a clinical diagnosis of FAD (known FAD mutation and dementia) who have a positive ASS PET scan (N=12), subjects with known FAD mutation but without clinical evidence of dementia (N=12) and healthy subjects (N=8) to determine if the tracer reliably reports on ASS status; and, (3) to begin constructing a database of AD and normal retinal images for use in developing automated, AI-assisted retinal biomarker analytics tools for physicians and researchers.
Completion of these aims will advance the development of our in vivo ocular diagnostic test, getting us one step closer to our mission of providing an antemortem, simple, and affordable diagnostic to parse the heterogeneity of AD. Future studies will integrate knowledge obtained from ongoing clinical studies of AMDX-2011P as a marker of A-SYN and TDP-43 and assess whether the tracer can report on the co-occurrence and variability of these critical biomarkers in individual patients.
Alzheimer’s disease (AD), the most common form of dementia, has traditionally been defined by the accumulation of amyloid beta (ASS) in neuritic plaques and hyperphosphorylated tau in neurofibrillary tangles. However, recent evidence indicates that AD is better viewed as a continuum of disease with a broader degree of mechanistic and pathological heterogeneity.
For example, ~15% of AD patients are negative for ASS and most AD patients have “mixed pathology”, with large subsets exhibiting accumulation of additional neurodegenerative biomarkers such as a-synuclein (A-SYN) and the TDP-43. Hippocampal and amygdalar deposits of TDP-43 have recently been characterized as defining a disease state that overlaps heavily with AD: limbic-predominant, age-related TDP-43 encephalopathy (LATE).
At present, AD diagnosis relies on clinical evaluation of symptoms and PET imaging of ASS and tau load. However, this is costly, involves exposure to radiation, and does not have the ability to detect broader dimensions of AD heterogeneity, such as the presence of pathological A-SYN and TDP-43 deposits that define large subsets of the AD continuum.
There is an unmet medical need for an antemortem diagnostic that can reliably identify mechanistic heterogeneity in individual AD patients, ideally one that can detect multiple disease-related biomarkers simultaneously and non-invasively in CNS tissue.
Amydis is leveraging the retina as a “window to the brain” to address this unmet need by developing an ocular contrast agent – i.e. a “retinal tracer – that can be used to fluorescently label A-SYN, TDP-43, and ASS in patients suspected of having AD. The retinal tracer, AMDX-2011P, currently in human clinical trials, has these remarkable capabilities and is designed to have fluorescent properties amenable for use with standard retinal imaging equipment found in the eye care office, making this technology widely accessible.
In this proposal, Amydis will take the first clinical steps towards developing transformative new diagnostic technology in AD focusing on the biomarker ASS in AD patient retinas. The specific aims of the project are: (1) to develop a lyophilized product of AMDX-2011P for I.V. delivery; (2) to complete a phase 1B clinical trial of AMDX-2011P in patients with a clinical diagnosis of FAD (known FAD mutation and dementia) who have a positive ASS PET scan (N=12), subjects with known FAD mutation but without clinical evidence of dementia (N=12) and healthy subjects (N=8) to determine if the tracer reliably reports on ASS status; and, (3) to begin constructing a database of AD and normal retinal images for use in developing automated, AI-assisted retinal biomarker analytics tools for physicians and researchers.
Completion of these aims will advance the development of our in vivo ocular diagnostic test, getting us one step closer to our mission of providing an antemortem, simple, and affordable diagnostic to parse the heterogeneity of AD. Future studies will integrate knowledge obtained from ongoing clinical studies of AMDX-2011P as a marker of A-SYN and TDP-43 and assess whether the tracer can report on the co-occurrence and variability of these critical biomarkers in individual patients.
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
California
United States
Geographic Scope
State-Wide
Related Opportunity
Analysis Notes
Amendment Since initial award the End Date has been extended from 08/31/25 to 08/31/26 and the total obligations have increased 101% from $1,704,372 to $3,420,052.
Amydis was awarded
Advanced Retinal Biomarker Database for Alzheimer's Heterogeneity
Project Grant SB1AG050454
worth $3,420,052
from National Institute on Aging in September 2015 with work to be completed primarily in California United States.
The grant
has a duration of 11 years and
was awarded through assistance program 93.866 Aging Research.
The Project Grant was awarded through grant opportunity SBIR/STTR Commercialization Readiness Pilot (CRP) Program Technical Assistance and Late Stage Development (SB1 Clinical Trial Required).
SBIR Details
Research Type
SBIR Phase II
Title
Use of novel fluorescent tracers to develop a comprehensive retinal biomarker database that maps the heterogeneity of Alzheimer's pathogenesis
Abstract
Project Summary Alzheimer’s disease (AD), the most common form of dementia, has traditionally been defined by the accumulation of amyloid beta (Aβ) in neuritic plaques and hyperphosphorylated tau in neurofibrillary tangles. However, recent evidence indicates that AD is better viewed as a continuum of disease with a broader degree of mechanistic and pathological heterogeneity. For example, ~15% of AD patients are negative for Aβ and most AD patients have “mixed pathology”, with large subsets exhibiting accumulation of additional neurodegenerative biomarkers such as α-synuclein (α-syn) and the TDP-43. Hippocampal and amygdalar deposits of TDP-43 have recently been characterized as defining a disease state that overlaps heavily with AD: Limbic-predominant, Age- related TDP-43 Encephalopathy (LATE). At present, AD diagnosis relies on clinical evaluation of symptoms and PET imaging of Aβ and Tau load. However, this is costly, involves exposure to radiation, and does not have the ability to detect broader dimensions of AD heterogeneity, such as the presence of pathological α-syn and TDP- 43 deposits that define large subsets of the AD continuum. There is an unmet medical need for an antemortem diagnostic that can reliably identify mechanistic heterogeneity in individual AD patients, ideally one that can detect multiple disease-related biomarkers simultaneously and non-invasively in CNS tissue. Amydis is leveraging the retina as a “window to the brain” to address this unmet need by developing an ocular contrast agent – i.e. a “retinal tracer – that can be used to fluorescently label α-syn, TDP-43, and Aβ in patients suspected of having AD. The retinal tracer, AMDX-2011P, currently in human clinical trials, has these remarkable capabilities and is designed to have fluorescent properties amenable for use with standard retinal imaging equipment found in the eye care office, making this technology widely accessible. In this proposal, Amydis will take the first clinical steps towards developing transformative new diagnostic technology in AD focusing on the biomarker Aβ in AD patient retinas. The specific aims of the project are: (1) to develop a lyophilized product of AMDX-2011P for i.v. delivery; (2) to complete a Phase 1B clinical trial of AMDX-2011P in patients with a clinical diagnosis of FAD (known FAD mutation and dementia) who have a positive Aβ PET scan (N=12), subjects with known FAD mutation but without clinical evidence of dementia (N=12) and healthy subjects (N=8) to determine if the tracer reliably reports on Aβ status; and, (3) to begin constructing a database of AD and normal retinal images for use in developing automated, AI-assisted retinal biomarker analytics tools for physicians and researchers. Completion of these aims will advance the development of our in vivo ocular diagnostic test, getting us one step closer to our mission of providing an antemortem, simple, and affordable diagnostic to parse the heterogeneity of AD. Future studies will integrate knowledge obtained from ongoing clinical studies of AMDX- 2011P as a marker of a-syn and TDP-43 and assess whether the tracer can report on the co-occurrence and variability of these critical biomarkers in individual patients.
Topic Code
NIA
Solicitation Number
PAR20-130
Status
(Ongoing)
Last Modified 8/20/25
Period of Performance
9/30/15
Start Date
8/31/26
End Date
Funding Split
$3.4M
Federal Obligation
$0.0
Non-Federal Obligation
$3.4M
Total Obligated
Activity Timeline
Transaction History
Modifications to SB1AG050454
Additional Detail
Award ID FAIN
SB1AG050454
SAI Number
SB1AG050454-2420061961
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
LCXNBB1KM9K9
Awardee CAGE
735B0
Performance District
CA-90
Senators
Dianne Feinstein
Alejandro Padilla
Alejandro Padilla
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) | $1,704,372 | 100% |
Modified: 8/20/25