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HIV Drug Resistance Target Find

A specific protein in the body may be the key to overcoming the increasing problem of resistance to HIV drugs. Inactivating the ITK protein which is involved...

30 Apr 2008
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A specific protein in the body may be the key to overcoming the increasing problem of resistance to HIV drugs. Inactivating the ITK protein which is involved in the immune response blocks many steps of HIV replication, studies in the laboratory show. Most current HIV drugs attack the virus itself which is liable to mutate and become resistant to treatment. HIV experts said the results were promising but any drug would take a long time to get to the clinic. ITK is involved in activating a type of immune cell called a T cell in the presence of infection. HIV works by infecting T cells, taking them over so they can replicate and create large quantities of the virus, compromising the whole immune system. The team at the US National Institutes of Health realised that many of the pathways regulated by ITK were also needed for HIV to take hold in the body. Tests in human cells in the laboratory showed that removing or inactivating ITK could, as predicted, block many different steps in the ability of HIV to enter a cell, spread and replicate, the study in Proceedings of the National Academy of Sciences showed. Drug development Dr Pamela Schwartzberg said each of the steps only had a small effect but together they were significant. What remains to be seen is how effective targeting ITK would be compared to existing drugs she said. But due to other research looking at the role of ITK in immune responses in asthma, there are already potential drugs in development. "Currently we have multiple options for treating HIV and we use multi-drug regimens but most of these therapies are directed against viral proteins which are subject to rapid changes allowing mutations to develop. "Our own cellular machinery is less prone to making mistakes. "ITK had an effect on HIV replication at several stages which if you add them up seems to be a profound effect." Professor David Back, an expert in HIV pharmacology at the University of Liverpool said development of drug resistance was the main problem with current therapy. "There is no question that we need new drugs acting on existing targets but also new drugs acting on new targets. "Consequently any glimmer that a target protein may be less susceptible to mutational changes is an exciting prospect - this study on ITK looks just that." However, he said there is a long road between proof of concept and a drug molecule ready for use in the clinic.
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Source: MJFM



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