Induction of Apoptosis by HIV Viral Protein, a New Target for Treatment of AIDS and Cancer
Since its discovery in the early 1980s, infection with HIV has reached epidemic proportions, especially in developing countries. Estimates suggest that 42 million people are living with HIV/AIDS worldwide, of whom around 3 million die each year. Current treatments involve a cocktail of drugs that effectively target two main HIV proteins. But these drugs can lose effectiveness when the virus mutates and becoming resistant. New drug targets within the HIV infection pathway would allow for a more robust treatment protocols. Dr. Planelles and colleagues at the University of Utah have discovered just that. They have discovered a compound that blocks HIV replication by targeting a specific cellular protein. A human gene named ATR normally protects people by preventing the replication of cells damaged by radiation or toxic chemicals through induction of a G2 of cell division checkpoint. They have shown however, in people infected with HIV, the Viral protein R (Vpr) hijacks ATR, preventing the replication of vital white blood cells. In addition to causing cell cycle arrest, Vpr activation of ATR also leads to cellular apoptosis through BRCA1 protein, which is directly involved in the repair of damaged DNA. This pathway represents a key target for future anti-HIV drug treatments.
The CDC estimates that approximately 40,000 persons become infected with HIV each year in the US only; with HIV prevalence is expected to reach 1.3 millions by 2010. The entire market for HIV treatment medications was about $6 billion in 2003, but the market may be worth double that by 2007.
Stage of Development
A PCT application with publication number WO0604695 A1 has been published and is pending.
This technology is part of an active and ongoing research program and has been demonstrated to work in proof-of-concept experiments. It is available for licensing under either exclusive or non-exclusive terms.
*Andersen JL, Zimmerman ES, DeHart JL, Murala S, Ardon O, Blackett J, Chen J, Planelles V. (2005) ATR and GADD45alpha mediate HIV-1 Vpr-induced apoptosis. Cell Death Differ. 12:326-34.
Vicente Planelles, Erik Zimmerman, Josh Andersen
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