Björn Schumacher receives Eva Luise Köhler Research Prize 2019: Rare diseases provide insight into the secret of ageing


Prof. Björn Schumacher Foto: Uniklinik Köln

"Childlike old people" and so-called "children of the night" - in general terms, impressive figures of speech have established themselves for those affected by a series of complex disease patterns caused by a congenital malfunction of the DNA repair mechanisms that have so far hardly been researched. Prof. Dr. Björn Schumacher from the CECAD Cluster of Excellence for Aging Research at the University of Cologne, one of the most distinguished researchers who is striving for a fundamental understanding of these processes, will now receive the Eva Luise Köhler Research Prize for Rare Diseases 2019, endowed with 50,000 euros. The award ceremony will take place on 26 February 2019 in Berlin.

Environmental influences, such as UV light or tobacco smoke, but also quite ordinary metabolic by-products, cause about ten thousand damages to the genetic material every day - in every single cell of the human body. Fortunately, cell repair systems, such as nucleotide excision repair (NER), were developed early in evolution to remove the damage that alters the double helix structure of DNA, for example.

"However, if such repair systems do not function properly right from the start due to certain congenital genetic defects, not only does the cancer risk of the affected persons increase considerably," explains the renowned children's endocrinologist Professor Dr. Annette Grüters-Kieslich, CEO of the Eva Luise and Horst Köhler Foundation for People with Rare Diseases and adds: "The effects of these disease patterns - such as Xeroderma pigmentosum (XP) or Cockayne Syndrome (CS), which have hardly been researched so far - are absolutely dramatic for the mostly very young patients in many respects.

The affected children age in fast motion and die early

The skin of "children of the night" - as XP sufferers used to be called because they have to avoid all UV radiation throughout their lives - is thousands of times more sensitive to UV radiation than that of healthy people. Without consistent protection, those affected often develop extremely severe burns after only a short period of exposure to the sun and develop skin cancer in the first few years of their lives.

The Cockayne Syndrome (CS), which is also very rare, is caused by a slightly different mutation in another gene that repairs DNA damage. This causes the affected children to age in fast motion: Already in the first years of life, the "young elderly" suffer from typical age-related complaints such as arteriosclerosis and a rapid decline in hearing and vision. Patients remain small and die before they reach teenage age because there is currently no therapy that goes beyond the treatment of the accompanying symptoms.

"In order to mitigate the dramatic effects of our fragile DNA, repair systems were developed early in evolution," said Professor Björn Schumacher. Therefore, the investigation of genes that have congenital defects in CS and XP has already provided his research group with a lot of information about such basic cell functions, explains the prizewinner: "Rare diseases provide us with insights into the secret of human aging.

The researchers reproduce the effects of the genetic defect in the nematode

In order to be able to investigate NER disease mechanisms in vivo, Professor Schumacher's research group developed a threadworm (C. elegans) as a model organism that carries the same genetic mutation that causes CS in humans. Such a simple animal model - after all, a human being weighing 70 kg has about 30 billion times more body cells than a threadworm - is invaluable for the investigation of highly complex clinical pictures.

The model organism showed that the malfunction of the NER repair mechanism does not lead to mutations that are passed on from cell division to cell division. Rather, the damage remaining in the genetic material hinders the reading of genes, a process essential for cell function. The cell reacts to the remaining DNA damage with a highly complex event cascade at the molecular level, at the end of which it stops its activity and dies. The body cannot develop, tissues and organs lose their ability to function. "Using our threadworm model, we were able to show that these damage-response mechanisms use certain signalling pathways that are controlled by insulin-like growth factors (IGF), for example. They are of central importance for aging - whether premature in CS or gradual in the course of the normal ageing process. As part of our project funded by the Eva Luise and Horst Köhler Foundation, we now want to look more closely at how we can have a therapeutic effect on the signalling chain," said Björn Schumacher confidently. In contrast to the highly complex mechanisms of nucleotide excision repair (NER), the signalling pathways are therapeutically attackable by certain drug substances, explains the prizewinner. Scientists in his research group at CECAD were able to restore tissue function and delay ageing even in nematode mutants that lacked the NER repair mechanisms.

Initial therapeutic approaches

The identification of these damage response mechanisms opens up new perspectives for the pharmacological treatment of progeroid hereditary diseases for which no therapeutics are currently available, the prizewinner hopes: "Our research could become a basis for realistic therapies that can be implemented in the future.

The Eva Luise Köhler Research Prize for Rare Diseases will be awarded for the twelfth time in cooperation with the Alliance of Chronic Rare Diseases (ACHSE).

The prizewinner:

Professor Dr. Björn Schumacher studied biology at the University of Constance and Stony Brook University in New York and received his doctorate at the Max Planck Institute for Biochemistry in Martinsried near Munich.

The molecular biologist is regarded as one of the world's most prominent researchers on ageing. His research group at the CECAD Cluster of Excellence for Aging Research at the University of Cologne focuses on nucleotide excision repair (NER), a mechanism that is responsible for the recognition and repair of damage in genetic information. Since January 2019, CECAD has been funded in the third funding period of the Excellence Strategy of the Federal Government and the Federal States and deals with the basics of various diseases of aging.