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FUGE-Funksjonell genomforskn.i Norg

Development of immunostimulatory therapy disrupting the hyperactivated cAMP signalling pathway in HIV immunodeficiency

Awarded: NOK 4.7 mill.

Project Number:

167203

Project Period:

2005 - 2007

Organisation:

Subject Fields:

LAURAS is developing immunostimulatory drugs that will reverse the immunodeficiency in HIV and other immunodeficiencies. Such treatment is called for since the present antiretroviral treatment (HAART) does not offer cure for the disease, is associated wit h resistance and has significant side effects. Immunostimulatory drugs could possibly assist the immune system in driving out the HIV virus and is expected to lower the incidence of opportunistic infections. LAURAS has shown that the cAMP/protein kinase A pathway (cAMP/PKA type I pathway) is hyperactivated in patients with HIV infection, leading to T cell dysfunction. It has been shown in vitro that the specific T cell dysfunction appearing in HIV patients may be reversed with cAMP antagonists. In vivo st uides in a murine AIDS model have also demonstrated significant effects of cAMP antagonists on T cell immune function. LAURAS has for the past three years been running a chemistry programme to develop PKA type I selective antagonists for PKA and brought f orward a whole series of new compounds, cAMP antagonists, that are currently being developed as tentative clinical candidates. To further improve these compounds, LAURAS would like to do rational, structure-based drug design to optimize binding and affini ty further and develop principles for drug delivery. Further development with regulatory studies on toxicology, animals and phase I, II and III clinical trials will have to be conducted after completion of this project in order to put a new drug on the ma rket. In addition, LAURAS would like to develop high throughput methodologies to be able to screen larger compound libraries to come up with empirical structures which are not based on the adenine and ribose moieties present in cAMP and which have been us ed in in the rational design approach. The present project will optimize the further development of selective inhibitiors of the cAMP/PKA type I pathway, which will contribute to a new treatment of HIV-infection

Funding scheme:

FUGE-Funksjonell genomforskn.i Norg

Thematic Areas and Topics

No thematic area or topic related to the project