Abstract
| Grant Number: | 2R44MH075211-02A1 |
| Project Title: | Novel Approaches to Blood Brain Barrier Function |
Abstract:
DESCRIPTION (provided by applicant): Central nervous system (CNS) - targeting drugs, such as antiretrovirals in the treatment of AIDS, need to cross the blood-brain barrier (BBB) in order to reach their therapeutic receptors inside the brain. A critical issue in the treatment of AIDS is that the HIV-1 virus can reside in hard-to-reach sanctuaries in the brain (mainly in macrophage cells). If a candidate molecule does not have the right physical properties to effectively cross the BBB, it cannot realize its therapeutic potential. Our proposal addresses this aspect, with two novel high-throughput assays for CNS drug transport across the BBB. In Phase I of the SBIR we developed a promising brain lipid (BL) parallel artificial membrane permeability assay (PAMPA), called BL-PAMPA, to predict the kinetic parameters, log PS (permeability-surface area product), measured by the in situ brain perfusion assay in P-glycoprotein deficient [mdr1a(-/-)] "knockout" mice. In Phase II, we will commercialize this brain lipid and other proprietary reagents. In Phase II, an additional high-throughput blood-brain barrier related assay based on binding gradients will be developed. The new assay will be used to predict rodent steady-state (pseudo-equilibrium) brain penetration, log BB. In our commercialization effort during the three-year Phase II period, we plan to design, make, and test (a) several proprietary reagent-containing buffers, (b) a special microtiter plate for endothelial cultured cell assays that account for the aqueous boundary layer effects, and (c) a blood brain barrier measuring instrument based on diode array UV spectrophotometry, which would increase the rate of data acquisition about 50 fold over currently available instruments.
Thesaurus Terms:
antiAIDS agent, artificial membrane, blood brain barrier, high throughput technology, membrane permeability, neuropharmacology, technology /technique development
biomedical equipment development, computer program /software, computer system design /evaluation, robotics, ultraviolet spectrometry
biotechnology, mixed tissue /cell culture
| Institution: | PION, INC |
| 5 CONSTITUTION WAY |
| WOBURN, MA 01801 |
| Fiscal Year: | 2007 |
| Department: | |
| Project Start: | 15-AUG-2005 |
| Project End: | 31-JUL-2010 |
| ICD: | NATIONAL INSTITUTE OF MENTAL HEALTH |
| IRG: | ZRG1 |
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