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New cAMP antagonists
Framework programme: 5
Project number:
EC contribution: € 945 844
Duration: 24 months
Starting date: December 2002
Graphic element Development of Antagonists that Disrupt the Hyperactivated cAMP Signalling Pathway in Immunodeficiencies as Immunostimulatory Therapy
Keywords: Immunotherapy; immunostimulatory drug; HIV; AIDS; immunodeficiencies; cAMP; protein kinase A type I (PKAI); T lymphocyte; antagonist


Drugs for immunomodulating therapy in HIV and other immunodeficiencies could possibly assist the immune system in driving out the HIV virus, and is expected to lower the incidence of opportunistic infections in several immunodeficiencies. The technology in the project is based on new knowledge showing that activation of a signal pathway involving the signal substance cAMP and protein kinase A type I, PKAI, inside white blood cells, T lymphocytes, inhibits the function of the immune system.
During HIV infection, the activity of this signal pathway is greatly increased due to elevated levels of cAMP and the function of the patient’s white blood cells is strongly reduced (Figure 1A). Development of immunostimulatory drugs that interfere with cAMP action by targeting and disrupting the cAMP/PKA type I signalling pathway will improve the immune function of T lymphocytes. The concept of developing PKAI selective cAMP antagonists that counteract cAMP action in T lymphocytes is demonstrated in Figure 1B. In vivo experiments and ex vivo clinical testing of compounds are on-going. The project will aim for treatment protocols that can help eradicate HIV and lower the total cost of treatment or simplify administration of the total treatment.


HIV causes a chronic infection leading to severe dysfunction of the immune system with markedly increased incidence of a large number of infections and ultimately death. In the EU, HIV infection is the fifth leading cause of death among young adults. In the developing world, this problem is even larger. Estimates by the World Health Organisation indicate that the total number of HIV positive patients by the end of 2001 was above 40 million (including more than 1 million in the EU). The current treatments of HIV include only drugs that target the virus. These potent cocktails of anti-HIV drugs have been successful in keeping AIDS at bay in HIV-infected people. However, although these combination therapies can knock the virus back to undetectable levels in patients’ blood, HIV continues to lurk in reservoirs containing immune cells that harbour the virus where the drugs cannot reach. Thus, the present therapy does not offer cure for the disease, requires life-long treatments and has significant problems with adverse events and development of resistance. Alternative HIV therapies are now called for, and research efforts are therefore focused at developing immunostimulatory treatments that in combination with present treatment have the potential of eradicating the virus.


The aim of the project is development and evaluation of immunostimulatory drugs that will reverse the immunodeficiency in HIV and other immunodeficiencies. Such treatment is called for since the present treatment does not offer a cure for the disease, is associated with 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 in several immunodeficiencies, such as common variable immunodeficiency, septicemia (commonly caused by nosocomial infections) and the immunodeficient state occurring in cancer-induced cachexia, as well as following administration of cytostatic drugs.

Potential applications

Treatment based on immunostimulation, which will improve the function of the immune system of patients, can make the immune system competent in driving out the virus from the reservoirs. This appears to be an attractive and important addition to the present treatment of HIV, which only offers antiretroviral drugs. Furthermore, immunostimulation may be a prerequisite for efficient therapeutic vaccination strategies to work effectively.


Wenche Marie Olsen
Lauras AS
0349 Oslo
Tel: +47 2295 8986
Fax: +47 2260 4427


Official Address Other Information
2Hans-G.GenieserBIOLOG Life Science Institute, Forschungslabor und Biochemica-Vertrieb GmbH
Flughafendamm 9a
DE-28199 Bremen
Tel: +49 421 591355
Fax: +49 421 5979713
3Bastian ZimmermanBiaffin GmbH & Co KG
AVZ 2, Heinrich-Plett-Str. 40
DE-34132 Kassel
Tel: +49 561 804 4661/-4662
Fax: +49 561 804 4665
4Jo Klaveness, Ph.D.Department of Medical Chemistry, School of Pharmacy, University of Oslo
P.O.Box 1068 Blindern
0316 Oslo
Tel: +47 2285 5043
Fax: +47 2285 7975
5Friedrich W. HerbergUniversität Kassel
FB 18, Abteilung Biochemie
Heinrich-Plett-Str. 40
DE-34132 Kassel
Tel: +49 561 804 4511 / 4161
Fax: +49 561 804 4466
6Kjetil TaskénThe Biotechnology Centre of Oslo, University of Oslo
P.O. Box 1125, Blindern
0317 Oslo
Tel: +47 2284 0505
Fax: +47 2284 0506
7Michel MoutschenUniversity of Liège
CHU Sart-Tilman
BE-4000 Liège
Tel: +32 4 366 2410
Fax: +32 4 366 2919

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