Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Human on a chip system to investigate genetic risk factors in Alzheimer's disease

Award Number: R43AG060886
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2018
PERIOD OF PERFORMANCE END DATE: 05/31/2022

Group Awards By:

View Award Description

Human on a chip system to investigate genetic risk factors in Alzheimer's disease - Project Summary/Abstract Hesperos will construct and test microscale multi-organ systems with recirculating blood and cerebral spinal fluid surrogates that will give insights to the responses of various Alzheimer’s phenotypes to drugs as well as the influence of peripheral effects on AD progression, specifically ApoE variants. We seek to leverage Dr. Morgan’s research on Alzheimer’s and aging combine it with Drs. Shuler and Hickman’s research on human-on-a-chip systems to better understand the disease and its mechanism of action and to test efficacy and toxic side effects of treatments. We will investigate both small molecules and biologics, on human organ modules in the same multi-organ system using iPSC derived non-diseased (ND) and Alzheimer’s phenotypes. A preclinical model that can accurately predict human response should not only lead to better decisions on which Alzheimer’s treatment to take into human clinical trials, but also for personalized medicine applications. By eventually comparing acute to chronic effects, the model will enable prediction of clinical trial success using pharmacodynamic (PD) models to inform clinical disease trials from preclinical studies. Current human-based in vitro toxicity studies have the limited capacity to predict functional changes that have been the demise of many potential therapeutics. We have previously constructed platforms demonstrating the integration of multiple organ mimics for acute responses and will build upon that technology. In this Phase I proposal we will build a 3-organ system composed of cortical neuronal components to utilize long term potentiation (LTP) as a functional readout, which will be separated by a functional blood brain barrier (BBB) from a liver model. The liver will result in a model with not only parental drugs but metabolites in the blood and the BBB will model the penetration of the drug and its metabolites into the brain. We will use isogenic methods to introduce the APP mutation into iPSCs and screen and select for ApoE3 and ApoE4 variants to test in the system vs. control. The effect of mutation and variant in both neurons and liver will give insight to peripheral as opposed to CNS effects. Development of a low cost, easy to use multi-organ system to assay drugs for AD would facilitate widespread usage and maximize the benefit to the drug development community as well as for efficacy and toxicological evaluations for patient specific treatment. The integrated use of these pre-clinical test systems and PBPK/PD models provides a powerful tool for evaluating the dynamic interaction between drugs, aging biological system and disease and will facilitate rationale drug development and clinical trial design. Our team contains all of the skill sets to achieve the goals on the grant. In Phase II, we will expand our experiments from acute to chronic and then extend this to AD patient specific samples for personalized medicine applications.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2019	HESPEROS, INC.	12501 RESEARCH PKWY STE 100	ORLANDO	FL	32826	ORANGE	USA	Aging Research	000	2	12/7/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	HESPEROS, INC.	12501 RESEARCH PKWY STE 100	ORLANDO	FL	32826	ORANGE	USA	Aging Research	000	2	5/13/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $335,252 )
2019	2019	HESPEROS, INC	3259 PROGRESS DR, # 158	ORLANDO	FL	32826	ORANGE	USA	Aging Research	000	2	5/30/2019	NON-COMPETING CONTINUATION	$335,252
														Subtotal = $335,252

Issue Date FY: 2018 ( Subtotal = $334,005 )
2018	2018	HESPEROS, INC	3259 PROGRESS DR, # 158	ORLANDO	FL	32826	ORANGE	USA	Aging Research	000	1	8/13/2018	NEW	$334,005
														Subtotal = $334,005

Grand Total All Awards = $669,257

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Human on a chip system to investigate genetic risk factors in Alzheimer's disease

Award Number: R43AG060886

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2018

PERIOD OF PERFORMANCE END DATE: 05/31/2022

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer