The DRUGSFORD project aimed at finding new ways to counteract hereditary photoreceptor degeneration.
The consortium consisted of two biotech companies and three academic research groups. BIOLOG Life Science Institute (Bremen, Germany) is a world leader in developing and producing compounds that interact with various cGMP-governed cellular reactions. The Dutch company BBB Therapeutics (Leiden, The Netherlands) has developed specialized drug delivery systems that help pharmaceutical substances pass across the blood-brain-barrier. The combined expertise of these two companies allowed the project to come up with novel drugs and ways to deliver them across the blood-retina-barrier, so that they can reach the photoreceptors. The academic research groups are connected to Valeria Marigo (University of Modena (Modena, Italy), Per Ekström (Lund University, Lund, Sweden) and François Paquet-Durand (University of Tübingen, Germany), and have already previously collaborated regarding photoreceptor degeneration mechanisms and the protective effect of treatments with various substances. The academic groups tested the drug and delivery systems for their protective effects on diseased photoreceptors and retinas.
Together, the DRUGSFORD consortium members aimed at having a photoreceptor protective drug and delivery system ready for initial clinical trials by the finalization of the project period.
The goal of OXYGREEN was to gather the knowledge on the functions of selected enzymes that use oxygen to perform industrially relevant reactions. This knowledge was applied for the development of enzyme tools of interest for industrial and biotechnological applications.
University of Groningen, BioInfoBank Institute, DSM, Graz University of Technology, RWTH Aachen, Evonik Rexim, Vienna University of Technology, University of Pavia, Enzyscreen, University of Dortmund, Dechema, BIOLOG Life Science Institute
Major diseases including cardiovascular and renal diseases, diabetes mellitus, obesity, diseases of the immune system, cancer and neurological disorders are caused or are associated with disturbances of compartmentalization cAMP signalling networks.
Key players in cAMP signalling are adenylyl cyclases (AC) synthesizing cAMP, phosphodiesterases (PDE) hydrolysing it, and A-kinase anchoring proteins (AKAP) tethering protein kinase A (PKA), the principal effector of cAMP, to cellular compartments. In a multidisciplinary approach based on postgenomic research, the project used established and novel cell lines to identify small 'druggable' therapeutic molecules derived from small molecule libraries which
i.) displace PKA, AKAPs and PDEs from their cognate intracellular location and
ii.) disrupt protein-protein interactions involving ACs, PDEs, AKAPs and PKA in cellular disease models.
The disease models represent cardiovascular diseases, nephrogenic diabetes insipidus (NDI), asthma, chronic obstructive pulmonary disease (COPD), AIDS, obesity, and schizophrenia. Screening of compound libraries were performed in living cells and in vitro with purified components of the cAMP signalling system. The aim was to identify the molecular targets of small molecules using established and to be developed tools and bioassays.
Cell signature responses to challenges with small molecules were monitored in order to gain mechanistic insight into the effects on the disease phenotypes and to anticipate side effects of identified substances. The small molecules could be valuable tools to investigate compartmentalised cAMP signalling. Moreover, this approach may lead to alternative strategies for the treatment of diseases associated with altered cAMP signalling that are not addressed effectively by conventional pharmacotherapy.