As a part of a research collaboration, scientists at the Sahlgrenska Academy at Göteborg University, Sweden, have developed a new drug candidate against HIV-infection. The new substance, named alphaHGA, will be tested on patients this year. In a thesis from the Sahlgrenska Academy, parts of the research essential for the performance of the clinical trial are presented.
At the end of 2004, approximately 40 million people were living with HIV-infection, most of them in southern Africa. Annually, approximately three million people die from the infection, many of them young. Despite huge efforts, there has been no success in developing a vaccine against HIV. However, a number of drugs are used for treatment of HIV-infected individuals. The drugs cannot cure an infected person, but can slow down the disease progression. There are about 20 drugs commercially available, but since the virus can develop resistance and since the drugs are associated with side effects, there is a need for new, safer drugs.
Elin Andersson, M.Sc, presents in her thesis studies showing that the compound GPG-NH2 inhibits HIV in culture.
“GPG-NH2 inhibited the virus by a new mechanism of action. The molecule prevented the virus from forming the correct structure, and was therefore active against HIV resistant to currently available drugs” says Elin Andersson.
She also showed that in culture, HIV developed resistance to drugs used on patients today, but not to GPG-NH2. GPG-NH2 was tested on HIV-infected patients in 2001. The effect on HIV showed in culture could however not be reproduced in patients. Elin Andersson and the other scientists have now shown that GPG-NH2 in itself did not inhibit the virus. Instead, it needed to be degraded and one of the products from degradation, a so-called metabolite, was the actual active compound. The metabolite was produced by enzymatic degradation in the viral cultures. This degradation of GPG-NH2 to the active metabolite, named alphaHGA, occurs in two steps by two different enzymes present in the medium used in the viral cultures.
In her thesis, Elin Andersson has identified the first of the two enzymes, which is present in human blood. The reason for the failure of GPG-NH2 to inhibit HIV in patients was that the second enzyme needed for activation of the compound to alphaHGA is not present in human blood.
Besides the Sahlgrenska Academy, Karolinska Institutet and Uppsala University in Sweden and the Regainstitute in Belgium are part of the research collaboration. As previously reported by the biotech-company Tripep AB, the new compound alphaHGA will be tested on HIV-infected patients this year.
From Swedish Research Council