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LiebLab - Andreas Lieb - +43-512-9003-71231 - andreas.lieb@i-med.ac.at 

orcid: https://orcid.org/0000-0001-9567-649X

linkedin: https://www.linkedin.com/in/andreas-lieb

Disease specific engineering of designer receptor gene therapies

The main research focus of the laboratory aims for preclinical development and optimisation of gene therapies for neurological disorders, like epilepsy, Parkinson’s disease, neuropathic pain, or multiple sclerosis. Refractory epilepsy and Parkinson’s disease are amongst the most common neurological disorders, with more than 21 million and 6 million patients worldwide, respectively. Despite huge efforts to investigate and develop novel treatment strategies, both diseases are still difficult to treat. Multiple gene therapeutic options targeting Parkinson’s disease or refractory epilepsy have already been explored. However, all of them are limited by specific disadvantages, which we aim to overcome by disease specific engineering of designer receptors. In recent years, we developed a biochemical autoregulatory gene therapeutic system targeting refractory epilepsy. This is only activated if the excitatory neurotransmitter glutamate rises pathologically and suppresses emerging seizures. In addition, we identified a novel licensed drug activating the currently available designer receptor exclusively activated by designer drugs (DREADD). This drug comprises a superior side effect profile, facilitating the translation of this technology. Together these major achievements highlight that custom engineering of disease specific designer receptors is indeed feasible and will help to develop technologies with maximised therapy efficacy and minimal risk of side effects. Although, we were already able to advance/develop gene therapeutic strategies for the treatment of refractory epilepsy, we consider the currently available options not ideal. We will therefore further develop new and enhance existing technologies. In addition, we will expand the on-demand engineering of designer receptor gene therapies to other neurological diseases, like Parkinson’s disease.

Current research projects and third-party funding

♦ FWF Stand-Alone Project (“Designer Receptor Gene Therapy constructed for Parkinson’s - DR-GeTuP”), from the Austrian science fund. (405 720.00 €)

https://www.fwf.ac.at/forschungsradar/10.55776/P33222

Grant-DOI 10.55776/P33222

♦ FWF Stand-Alone Project (“TARGET- TARgeted Gene therapy for Epilepsy Treatment ”), from the Austrian science fund. (404 305.00 €)

https://www.fwf.ac.at/forschungsradar/10.55776/P35579

Grant-DOI 10.55776/P35579

Publications

Collaboration Partners

• Assist. Prof. Teresa Kaserer, Department of Pharmaceutical Chemistry, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria

• Prof. Dimitri Kullmann, Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom

• Dr. Tawfeeq Shekh-Ahmad, Department of Pharmaceutics, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel

• Assist. Prof. Janosch Heller, School of Biotechnology, Dublin City University, Dublin, Ireland

• Prof. Regine Heilbronn, Department of Virology, Campus Benjamin Franklin, Charité – Medical School, Berlin, Germany

• Prof. Nadia Stefanova, Section of Clinical Neurobiology, Department of Neurology, Medical University Innsbruck, Innsbruck, Austria

• Prof. Christoph Schwarzer, Institute of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria

• Assist. Prof. Dr.phil. Christian Vogl, Institute of Physiology, Medical University of Innsbruck, Innsbruck, Austria

• Assist. Prof. Bakk.biol. Victoria Franziska Klepsch M.Sc. PhD, Insitute of Cell Genetics, Medical University of Innsbruck, Innsbruck, Austria

• Assist. Prof. Dr.techn. Dipl.-Ing. Monika Cziferszky, Department of Pharmaceutical Chemistry, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria