In vivo expansion of human hepatocytes in Fah-/-Rag-/-Il2rg-/- mice

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$325,496.00
Award Year:
2010
Program:
STTR
Phase:
Phase I
Contract:
1R41RR028190-01
Award Id:
n/a
Agency Tracking Number:
R41RR028190
Solicitation Year:
2010
Solicitation Topic Code:
NCRR
Solicitation Number:
PA09-081
Small Business Information
3181 SW SAM JACKSON PARK RD, L321, PORTLAND, OR, 97239-3098
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
801452249
Principal Investigator:
MARKUSGROMPE
(503) 494-6888
grompem@ohsu.edu
Business Contact:
HONGXIANGLAN
(503) 494-6889
lanh@ohsu.edu
Research Institute:
Oregon Health And Science University

3181 SW Sam Jackson Pk Rd
PORTLAND, OR, 97239-3098
() -

Abstract
DESCRIPTION (provided by applicant): The liver is the site of many metabolic processes, including metabolism of xenobiotics such as pharmaceutical compounds. Drug metabolism is highly species specific and can vary significantly between individuals of the same species. To date no reliable experimental system capable of predicting the human-specific metabolic conversion of candidate small molecules exists. Our company (Yecuris Inc.) has developed an in vivo genetic selection system (the FRG mouse) that permits extensive humanization of murine liver by transplanted human hepatocytes. Preliminary data show that highly humanized mice (gt80%) accurately reflect most aspects of human drug metabolism. Therefore highly humanized FRG mice are an attractive novel system for modeling human drug metabolism and pharmacokinetics at an early stage of drug development. However, the extent of liver humanization achieved in our mice currently remains highly variable, ranging from lt 5% to gt90%. In order to make our platform more attractive to commercial customers and more commercially viable (reduced production cost per mouse), it will be necessary to reproducibly achieve high humanization levels in the majority of mice. In this phase 1 STTR application we propose 2 specific aims to advance our goal of reliable liver humanization: 1) We will test different background strains of mice for their ability to support high level liver repopulation. 2) The effects of different regimens to deplete/inhibit hepatic Kupffer cells on repopulation levels will be ascertained. PUBLIC HEALTH RELEVANCE: The animal model is an attractive novel system for modeling human drug metabolism and pharmacokinetics at an early stage of drug development. Commercialization of our technology will greatlyreduce the cost of and accelerate new drug development, thus contributing to public health.

* information listed above is at the time of submission.

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