Rare diseases affect children and adolescents in eight out of ten cases. Their participation in medical progress therefore depends crucially on committed pediatricians who are dedicated to the balancing act between bedside and laboratory. In order to prepare pediatric researchers for this demanding task and to provide them with the necessary freedom for scientific work at a high level, the research network Alliance4Rare initiated by the Eva Luise and Horst Köhler Foundation focuses among other things on structured Clinician Scientist Programs (CS4RARE). These programs provide participants with protected research time in which they can advance scientific projects on rare diseases without having to perform clinical tasks.
Some of the fellows who have recently started their work will introduce themselves and their projects.
Dear Dr. Knopf, you have been selected for the Clinician Scientist Program of Alliance4Rare. What motivated you to take this particular path in science and clinical practice?
During my residency training at a large pediatric hospital, I came into contact with rare diseases early on, including diseases of the immune system. During my training as a pediatric rheumatologist, my focus was on autoinflammatory diseases - both the genetically defined entities and those that can only be classified phenotypically. In children and adolescents with these complex phenotypes, autoinflammation and autoimmunity cannot always be clearly separated. To better understand the impaired regulation of inflammatory pathways, I have become increasingly involved with the topic of immune dysregulation and immune deficiency.
Since March 2022, I have been working with great enthusiasm in pediatric immunology and in an interdisciplinary team. There is a close connection between clinical work and research, which makes the subject so interesting. New disease-causing variants are constantly being found and new disease entities are being described. Thus, the number of definable diseases of the immune system is increasing every year. This is reflected, among other things, in the expansion of the groups in the classification of the International Union of Immunological Societies (IUIS), which was recently expanded to include the monogenetic autoinflammatory entities and diseases with bone marrow failure.
What are you currently working on and what would you like to achieve?
Currently, I work at the University Center for Rare Diseases (USE) and in the Department of Pediatric Immunology at the University Hospital Carl Gustav Carus at the TU Dresden.
My research focus is on autoinflammatory diseases and the search for new biomarkers to predict disease relapses and to improve therapy management. Among other things, we are analyzing gene expression in children with SURF (systemic undefined recurrent fever) in collaboration with colleagues from Würzburg and Luxembourg.
I very much hope that by establishing new biomarkers in combination with exome or genome diagnostics, we will accelerate the diagnosis of these diseases, which are generally very rare and in some cases difficult to diagnose. This will enable us to provide the children with targeted therapy more quickly.
What opportunities does the support provided by the Alliance4Rare Clinician Scientist Program open up for you in your day-to-day work which you would not have otherwise?
The Alliance4Rare offers me the unique opportunity to devote sufficient time to complex patients, in addition to my specialist work in the special consultation hour or in my campus-wide consultative work, in order to accelerate the diagnosis of a rare disease. Just this week, we were able to diagnose an autosomal recessive inherited disease in an adolescent, which will open up new therapeutic avenues and, in the future, enable the affected person to enjoy a better quality of life with fewer inpatient stays and reintegration into everyday education.
Without this funding, it would not be possible for me to take care of the functional evidence in vitro for gene variants that have not yet been described and not - as in the past - "file away" the unclear finding in the file. This is because the exclusion of a monogenetic rare disease is also important information for the patient and the practitioner.