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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44MH075211-02A1
Application #
7282850
Study Section
Special Emphasis Panel (ZRG1-BST-Z (10))
Program Officer
Grabb, Margaret C
Project Start
2005-08-15
Project End
2010-07-31
Budget Start
2007-09-15
Budget End
2008-07-31
Support Year
2
Fiscal Year
2007
Total Cost
$442,341
Indirect Cost
Name
Pion, Inc
Department
Type
DUNS #
968364430
City
Woburn
State
MA
Country
United States
Zip Code
01801