Project managers: PD Dr. A. Neubert, Prof. Dr. Dr. W. Rascher
Newborns and infants are particularly at risk for adverse drug reactions and medication errors due to common off-label use and lack of age-appropriate formulations. We have been working for many years on methods to improve medication safety. Data on adverse drug reactions (ADR) have been collected systematically; high-risk medications were detected and particularly vulnerable groups of patients were identified. We are currently investigating the impact of electronic prescription on medication safety, aiming at developing evidence-based, structured dosing information to be integrated into the prescribing system (AVOID). Moreover, our hospital is leading the organization of the “AMTS-Aktionsplan 2013-2015” item 16: Development of recommendations for the use of drugs in children particularly in the inpatient care. We actively participate in several EU-funded multicenter pharmacovigilance studies (e. g. long-term safety of the iron-chelating agent deferiprone and long-term safety of methylphenidate in children with ADHD). Furthermore, an EU-funded multicenter phase III study – coordinated by our hospital – is being conducted to investigate the use of clonidine as sedative agent in pediatric intensive care units (CloSed). In addition, we are also engaged in the EU-funded project "GAPP" which explores the efficacy and safety of gabapentin in neuropathic pain. The aim of both projects is a pediatric-use marketing authorization of the studied drugs.
Project managers: Prof. Dr. A. Hartner, PD Dr. K. Benz
Our research aims at elucidating the consequences of an early impairment of organ development for the pathogenesis of diseases during adolescence and adult life. To this purpose, the sequelae of a congenital reduction of nephron numbers or disruption of renal development for the kidney and the cardiovascular system are being studied. We have been focussing on the pathogenic mechanisms of inflammatory renal disease, hypertension, and heart failure. In further studies we are attempting to clarify which placental alterations may lead to defects in organ systems of the offspring and can expedite the onset of later disease. These studies are being performed in collaboration with the Perinatalzentrum Franken.
Project manager: Prof. Dr. H Schneider
Our primary research goal is to identify pathogenetic mechanisms underlying genodermatoses (hereditary disorders of the skin and its appendages) at a molecular level and to develop appropriate therapeutic approaches. These diseases are rare, but may be associated with life-threatening complications already in the first weeks after birth. In addition to the skin, other organs, such as eye, ear, and lung, are frequently affected by pathogenetic processes. First systematic studies of patients of different age groups allowed the characterization of genotype-phenotype relationships as a prerequisite for specific therapeutic attempts. In mouse models of epidermolysis bullosa, lamellar ichthyosis, and hypohidrotic ectodermal dysplasia, we have been investigating the feasibility of gene therapy in utero or perinatal protein replacement therapy. In September 2013 we started the first clinical trial in neonates with hypohidrotic ectodermal dysplasia, a multicenter interventional study based on the promising preclinical data collected over the last years.
Project managers: Prof. Dr. M. Metzler, Prof. Dr. T. Langer (until 06/2013)
Modern molecular biology has advanced understanding of the impact of both heritable and acquired genetic alterations on the development and progression of pediatric tumors. We have been trying to exploit such new information for diagnostic purposes and novel therapeutic approaches, placing emphasis on acute and chronic childhood leukemia, non-Hodgkin lymphoma, Ewing's sarcoma, and other frequent pediatric malignancies. In addition to acquired mutations in the tumor genome, the impact of hereditary single nucleotide polymorphisms on the development of late adverse effects of current cancer therapy, such as hearing loss or cardiomyopathy, is being investigated. Rare tumor entities have been recorded in the German Pediatric Rare Tumor Registry (STEP), which is located in our hospital, and have been further characterized in scientific projects.
Project managers: Prof. Dr. M. Rauh, Prof. Dr. H. Schneider
To clarify the origin of osteoprogenitor cells and the role of certain signaling molecules during skeletal development, we have been using a broad spectrum of methods including immunohistochemical approaches, gene expression assays, special cell culture systems, and determination of various enzyme activities by mass spectrometry. A related research project is focused on the controlled differentiation of cord blood-derived mesenchymal stem cells into osteoblasts and chondrocytes. These cells could be used for autografts, e.g. in the treatment of cleft lip and palate (the most common congenital malformation) to reduce the number of surgical interventions required.
Project manager: Prof. Dr. R.Trollmann
Aiming at an early detection and prevention of perinatal brain injury caused by acute or chronic hypoxia, we have been analyzing the regulation and function of hypoxia-inducible transcription factors (HIF) in the immature brain. HIF-regulated factors with strong impact on the adaptation to hypoxic conditions have been characterized as placental indicators of severe hypoxic-ischemic CNS injury in term neonates. In a mouse model of perinatal brain hypoxia, gestational age-dependent and cell-specific molecular effects of hypoxia on endogenous neuroprotective mechanisms have been demonstrated. Furthermore, the impact of perinatal hypoxia on early neuronal migration, astrocytic, and blood-brain barrier function has been investigated - as well as experimental approaches to stabilize HIF by pharmacological means.