Drug resistance is one of the most formidable challenges researchers face in designing viable treatment strategies to combat HIV, the virus that causes AIDS. Researchers have discovered yet another hurdle hindering effective treatment, but this one is attributable to the body itself. NIGMS grantee Dr. Richard Kim of the Vanderbilt University School of Medicine has found that a protein that resides in the brain�s protective blood-brain barrier, called P-glycoprotein, prevents the access of HIV protease inhibitor drug molecules into the brain, creating a safe haven in which the virus can thrive. Dr. Kim and his colleagues discovered that brain concentrations of protease inhibitors were much higher in mice lacking the P-glycoprotein gene.
The good news is that simply devising means to block this protein, which acts as a "pump" that ejects molecules out of the cell, could eliminate the molecular roadblock and permit the entry of protease inhibitor drugs to attack viral particles in the brain. As it happens, the pump is a rather ubiquitous dweller, nestled within cell membranes of various tissues in the body. Its presence in cancer cells thwarts many chemotherapeutic drugs� action by similarly denying them access. Because researchers have known about the presence of P-glycoprotein in cancer cells for over a decade, many potential drugs to block this pump are already in the pipeline.
Kim RB, Fromm MF, Wandel C, Leake B, Wood AJJ, Roden DM, Wilkinson GR. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J. Clin. Invest. 1998;101:289-94.
Reporters may call the NIGMS Office of Communications and Public Liaison at (301) 496-7301 to obtain the name of a scientist in the NIGMS Division of Pharmacology, Physiology, and Biological Chemistry who can comment on this work.
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8/9/2018 5:29 PM
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