This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Tauroursodeoxycholic acid (TUDCA) is a bile acid that has shown promise as a neuroprotective agent in rodent models of retinal degeneration and neurodegenerative disease. However, there are no studies showing target organ benefit with oral dosing. Before full-scale studies are undertaken in human patients with retinal disease, we need to better understand the pharmacokinetics and pharmacodynamics of the orally dosed compound in a relevant animal model. This study has the goal of identifying a potentially therapeutic dose and dosing regimen of TUDCA. Specifically, we propose to determine an oral dose that, at steady state plasma concentration, achieves a retinal level found to be therapeutic in rodent studies, and further, to determine whether vitreous and CSF levels can function as surrogates for retinal levels of TUDCA. The animal of choice is the rhesus macaque because of the similarity in bile acid metabolism and retinal physiology in humans and nonhuman primates. The study will provide key information needed for the design of clinical trials in human patients with retinal degenerative diseases.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000163-52
Application #
8357872
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
52
Fiscal Year
2011
Total Cost
$43,647
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
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