Friday, July 20, 2012

New drug has the potential to eliminate HIV infection

When it comes to viral infections, HIV is the most well-known. It causes AIDS, resulting in the death of many cells of the immune system, leaving the body vulnerable to secondary infections. It is hard to treat, even though recent years have seen the development of various anti-viral drugs. AIDS is still not curable, and while the progress of the disease can be delayed, patients still die relatively young because of secondary infections. A new drug could possibly be the answer, as scientists have shown that it has the potential to kill all HIV-infected cells.

A naturally occurring compound called Cortistatin A was the foundation on which the scientists based their drug. This molecule was previously isolated from marine sponges, and had already been shown to be promising. Because it is impossible to keep harvesting Cortistatin A from these sea animals, scientists set up systems in order to synthetically produce the compound and turn it into an actual drug. At the Scripps Research Institute they proved to be successful, after which they proceeded with experiments to test its efficacy in lab-grown cultures of HIV-infected cells.
The structure of Cortistatin A.
Tests were performed with so-called CD4+ cells, which are lymphocytes (or white blood cells) and part of the immune system. Normally, they aid with setting up the immune response required to clear the body of 'foreign invaders', but if HIV succeeds, these cells die off and the patient develops AIDS. After setting up experiments with infected CD4+ cells, the scientists administered their synthetically produced Cortistatin A, and found it to be extremely effective. The production of new viruses declined by 99,7 percent, virtually eliminating the infection.

Cortistatin A is more effective than general anti-viral drugs, because it has the capability to block viral reproduction in cells that are already infected with HIV. It does that by binding to a HIV protein called Tat, which the virus needs to switch on its reproduction systems. Normally, drugs only block new cellular infections, meaning HIV can maintain its existence. The mechanism explains why Cortistatin A is much more efficacious, and because it already has a 'drug-like structure', development of the compound into an actual drug formula may not take long.

The experiments show that treatment with Cortistatin A looks extremely promising, also because it is effective in low concentrations and has no associated toxicity. However, a lot more research is needed before this finds its way into the clinic. So far, scientists have only tested the compound on cell cultures, and it remains to be seen whether the same effect will be found in live animals. Only after establishing efficacy in animals, can the first human trials begin. Because of its efficacy in the lab, it is likely that the first tests with animals will be set up rapidly.

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