Projects
Research interests
1. Studies on pathogenesis of HIV-associated neurocognitive disorders (HAND)
HIV infection causes neuropsychiatric complications manifesting in HIV-associated neurocognitive disorders (HAND). They occur in various forms in up to 60% of the HIV- infected population in the western world and affect medication adherence. We study the pathogenetic mechanisms involved in these disorders and especially the role of the regulation of the neurotransmitter dopamine on phenotype and progression of the disease. A current focus of our work is specifically the influence of genetic polymorphisms which modulate dopaminergic neurotransmission on the prevalence/frequency of HIV immunodeficiency infection in cohorts of German and African HIV-infected drug-naïve and antiretroviral therapy (ART)-medicated people.
BMBF-KI0211 Competence Network HIV/AIDS; DFG-GRK 1522
Cooperation with Prof. G Arendt (Dept. Neurology, University of Düsseldorf); Prof. IW Husstedt (Dept. Neurology, Universtiy of Münster); Prof M Maschke, Prof M. Obermann (Dept. Neurology, University of Duisburg); Prof. P Riederer (Dept. Psychiatry, University of Würzburg); PD S Sopper (IFTZ University of Innsbruck); Dr S du Plessis (Dept. Psychiatry, University of Stellenbosh, South Africa); Prof J Joska (Division Neuropsychiatry, University of Cape Town, South Africa)
1.1 Experimental model: SIV-infected rhesus monkeys (Macaca mulatta)
-Characterization of the functional consequences of SIV infection on specific neuronal populations/brain regions
-Mechanisms underlying specific neuronal/glial dysfunction and neurodegeneration: focus on dopaminergic/glutamatergic pathways
-Research on interactions between the immune system and the CNS
-Pharmacological treatments to elucidate mechanisms of dopamine action
1.2 Studies in HIV-infected humans
-Characterization of the consequences of HIV infection on dopaminergic systems
-Impact of dopamine on HIV infection and immune activation
-Dopamine genetic polymorphisms and their consequences on frequency and progression of HIV infection
-Autoimmunity and HIV
2. Studies on lithium carbonate as adjunctive treatment for HIV-associated neurocognitive disorders (HAND)
Sub-Saharan Africa is the area with the majority of HIV infections worldwide. Although antiretroviral therapy (ART) improves neuropsychiatric performance in a lot of patients with HAND, the prevalence of people with HAND increase. As the social and economic burden of HAND is great, there is an urgent need to identify effective adjunctive treatments for HAND. We conduct a randomized double blind placebo controlled trial to determine as primary endpoints the efficacy, safety and tolerability of lithium in patients with clade C-HIV with HAND stabilized on ART as well as to study the effect of lithium on proteins and genes associated with dopaminergic activation and biomarkers.
European & Developing Countries Clinical Trials Partnership (EDCTP) strategic primary grant SP. 2011.41304.065
Cooperation with: Prof J Joska (speaker of the EU grant, Division of Neuropsychiatry, University of Cape Town, South Africa); Dr EH Decloedt (co-investigator, Clinical Pharmacology, University of Cape Town, South Africa); Prof G Maartens (co-investigator, Clinical Pharmacology, University of Cape Town, South Africa); Prof S Lovestone (co-investigator, Institute of Psychiatry, King College London, United Kingdom)
