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A D osteoarthritis model targeting patient populations with high risk genetic polymorphisms

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43AR072166-01
Agency Tracking Number: R43AR072166
Amount: $225,000.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NIAMS
Solicitation Number: AR17-005
Timeline
Solicitation Year: 2017
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-09-01
Award End Date (Contract End Date): 2019-08-31
Small Business Information
2608 ERWIN RD, STE 19A
Durham, NC 27705-4597
United States
DUNS: 783502466
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 VINCENT WILLARD
 (919) 912-9839
 vincent.willard@cytextherapeutics.com
Business Contact
 BRADLEY ESTES
Phone: (919) 912-9839
Email: bradley.estes@cytextherapeutics.com
Research Institution
N/A
Abstract

Abstract
Osteoarthritis OA is a degenerative joint disease that affects an estimated million adults in the United
States and results in an economic burden of over $ billion per year Although the burden of OA is immense
current non surgical treatments are only palliative and no disease modifying OA drugs DMOADs presently
exist to address the problem This lack of success in identifying DMOADs is frequently attributed to the variable
causes of OA initiation and the dearth of human cartilage available for screening potential DMOADs To
increase the likelihood of identifying DMOADs we propose to study a segmented OA population based on
defined genetic predisposition to OA development To produce a nearly unlimited source of human cartilage for
use in DMOAD screening we will use induced pluripotent stem cells iPSCs as a cell source for cartilage
tissue engineering The goal of this project is to create a platform screening technology to identify the
therapeutic requirements of OA associated genetic risk factors Our approach is to create a three dimensional
in vitro model of OA which utilizes iPSC lines that have been modified to contain defined genetic variations In
Aim we will employ genome editing technology to generate OA associated single nucleotide polymorphisms
SNPs in the genome of hiPSCs Engineered cartilage formed from these edited cells will be characterized
using biochemical and micromechanical assays and then treated with inflammatory cytokines to induce OA like
changes in the cartilage The resulting in vitro OA model will be validated by measuring matrix degradation
loss of mechanical properties and production of inflammatory mediators In Aim our iPSC based model of
OA will be transferred to a well plate format to facilitate the development of an OA drug screening platform
A set of model therapeutics known to inhibit inflammatory degradation will be used to validate the sensitivity of
the model and to define high throughput readouts of OA progression Finally two libraries of novel bioactive
compounds will be screened for their ability to slow OA associated degradation in our in vitro model This
proposal will help elucidate the mechanism by which genetic variants result in increased risk for OA and will
catalyze the development of tailored OA therapeutics by providing a platform technology for identifying
therapeutic effectiveness based on defined risk factors Narrative
Osteoarthritis OA is a common cause of pain and disability but unfortunately there are no drugs available to
slow or stop progression of the disease This project will develop a bench top model of arthritis for rapid drug
testing based on a patient s genetic risk factors The long term goal is to identify effective drugs that can be
targeted to specific populations of OA patients

* Information listed above is at the time of submission. *

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