Prof. Dr. Malte Spielmann (UKSH): Next-Generation Genomics – A Cornerstone in Rare Disease Diagnostics
The diagnostic capabilities for congenital, genetically based rare diseases are advancing at an impressive pace. And yet, a sobering reality remains: more than half of patients suspected of having a rare disease still do not receive a definitive diagnosis.
Prof. Dr. Malte Spielmann, Director of the Institute of Human Genetics at University Hospital Schleswig-Holstein, provided insights in his presentation into the findings already made possible through currently established routine diagnostics and into the future potential opened up by emerging technologies.
As an example, he cited the genomDE pilot project, which is testing the implementation of whole genome sequencing under statutory health insurance coverage. But his perspective went further: with the next generation of technology—long-read sequencing—it may soon become possible to capture even more complex genetic relationships.
While initial results have so far shown only a modest diagnostic gain, the method remains promising particularly with regard to variants in non-coding regions, whose structural interactions can influence gene expression without altering the genes themselves.
Prof. Dr. Mehul Dattani ((UCL Great Ormond Street Institute of Child Health, London) : „Unravelling of a Rare Endocrine Disorder: Congenital Hypopituitarism“
Professor Mehul Dattani, Head of Paediatric Endocrinology at Great Ormond Street Hospital for Children, focused his presentation on congenital hypopituitarism, a rare disease in which specific regions of the central nervous system—namely the hypothalamus and the pituitary gland—do not function properly even before birth. The consequences are wide-ranging: from hormone deficiencies and severe developmental disorders to visual impairments and neurological symptoms.
Using recent studies and his own research findings, he demonstrated how modern genetic analyses are helping to better understand these complex clinical pictures.
It was particularly striking how he used mutations in the gene TBC1D32 to illustrate the role individual genes play in early brain development and how such discoveries can help explain even atypical or previously unclear disease courses. Mehul emphasized the importance of precise diagnosis and individualized genetic testing for affected children and their families not only for medical treatment, but also for counseling, prognosis, and day-to-day support.
“These conditions are often more complex than they appear at first glance and we must be willing to think beyond traditional disease categories,” he concluded.
This scientifically grounded yet practice-oriented presentation clearly demonstrated: precision medicine begins with close observation and the commitment to systematically explore what is still unknown at the molecular level.
Prof. Dr. Hildegard Büning (MHH): „Redefining Treatment: Innovations in Gene and Cell Therapies“
Prof. Dr. Hildegard Büning, Professor of Experimental Cell and Gene Therapy and Deputy Director of the Institute of Experimental Hematology at Hannover Medical School, provided an impressive overview of the current state of gene and cell therapy, emphasizing why now is the time to bring these technologies into broader clinical use.
Whether it is Zolgensma for the treatment of spinal muscular atrophy or CAR-T cell therapies for certain types of cancer: the first gene therapies have already been approved, and their clinical efficacy is well established. However, the path to widespread implementation remains challenging. Key hurdles include high treatment costs, complex manufacturing processes, and limited efficiency in certain target tissues.
This is precisely where Professor Büning and her team’s research comes in. Using capsid engineering—the targeted molecular modification of viral shells—future gene therapies can be directed even more specifically toward the desired tissue. The goals: improved efficacy, reduced immune responses, lower vector doses, and ultimately safer and broader access for patients.
“Gene therapy is fulfilling its promise,” was Büning’s clear message. But only if we continue to strengthen its foundation through joint action by science, healthcare, and policy.
Prof. Dr. Jan Baumbach (UKE Hamburg): „Privacy-preserving Multi-center AI – A Prerequisite for Rare Disease Research“
Prof. Dr. Jan Baumbach, Chair of the Computational Systems Biology lab at the University of Hamburg, delivered an impressive presentation on how federated artificial intelligence (AI) and systems medicine approaches can work together to advance personalized therapies for rare diseases.
A key concept was the identification of so-called druggable targets, molecular structures directly involved in disease development that can be addressed through pharmacological intervention. Rather than focusing on individual conspicuous genes, the models analyze entire networks and identify disease-relevant modules, which are treated as functional units.
This method makes it possible to reveal subtle disease mechanisms even when conventional statistical approaches fail. It is combined with a privacy-preserving infrastructure: on the FeatureCloud platform, AI models are trained decentrally across multiple locations without sensitive patient data ever leaving their original sites. This allows for the analysis of small and distributed case numbers, which is a critical advantage in rare disease research.
The presentation concluded with a forward-looking perspective on digital twins and generative AI, which could one day dynamically support therapy decisions.
Insights into the individual sessions of the 9th Rare Disease Symposium can be found here:
Keynote: „Unlocking the Secrets of Rare Diseases: How Precision Medicine is Turning Discovery into Hope“
Session 1: Case Study Neuronale Ceroid-Lipofuszinose (NCL)
Session 2: Unlocking the Power of Data in Rare Diseases
Session 4: Looking ahead: Visions and Advances for Tomorrow’s Healthcare of Rare Diseases
Photos: Andrea Katheder
We extend our heartfelt thanks to our partners for their financial support: Pfizer Pharma GmbH, Takeda Pharma Vertrieb GmbH & Co. KG, Sanofi-Aventis Deutschland GmbH, Alexion Pharma Germany GmbH, Chiesi GmbH, Ipsen Pharma GmbH, UCB Pharma GmbH, and PTC Therapeutics Germany GmbH.
