Targeted activation of ‘genetic self-help’: Eva Luise Köhler Research Award for Didier Stainier

Foundation of the former German President and his wife honours innovative therapeutic approach for Duchenne muscular dystrophy

Didier Stainier, Director at the Max Planck Institute for Heart and Lung Research in Bad Nauheim, has been awarded this year's Eva Luise Köhler Research Prize for Rare Diseases by the Eva Luise and Horst Köhler Foundation. The prize honours Stainier and his team for their basic research into the muscle disease Duchenne muscular dystrophy.

The foundation established by and named after Eva Luise Köhler and former German Federal President Horst Köhler, who passed away a few months ago, is dedicated to research into so-called rare diseases. A disease is categorised as rare if it affects fewer than one in 2000 people. These diseases are often not the focus of science and pharmaceutical companies, meaning that there are often few or no treatment options. The foundation aims to support and promote research into these particular diseases, thereby helping to open up new treatment options for the approximately five million people affected in Germany.

This year, Professor Dr Didier Stainier, Director of the Department of Developmental Genetics at the Max Planck Institute for Heart and Lung Research, together with his team members Dr Christopher Dooley and Lara Falcucci, will receive the Eva Luise Köhler Research Award for Rare Diseases, which is endowed with 50,000 euros. Their research project on the therapeutic use of transcriptional adaptation was honoured.

Transcriptional adaptation is a genetic protection mechanism with which cells can compensate in some cases for the loss of individual genes and thus at least partially maintain the function of the cell and organ. The Max Planck scientists have now been able to demonstrate this natural compensation mechanism for the first time in human cells of patients with Duchenne muscular dystrophy (DMD). This mechanism is based on the degradation of the mutated, non-functional dystrophin mRNA, which leads to the activation of functionally related genes such as utrophin. This can partially restore muscle cell function.

‘The model that presumed mRNA decay fragments can actively contribute to the regulation of related genes is tantamount to a paradigm shift and would fundamentally expand our understanding of genetic processes,’

says Stainier, categorising the study published in the journal Nature.

Targeting genetic compensation: a paradigm shift in the treatment of rare diseases

Professor Dr Annette Grüters-Kieslich, Chairwoman of the Eva Luise and Horst Köhler Foundation, explains: ‘The work of Professor Stainier and his team is of outstanding scientific quality and offers the potential to fundamentally change the therapeutic landscape for genetic rare diseases.’ The targeted use of the body's own compensatory mechanisms opens up new, previously unused avenues. This is particularly true where previous therapeutic approaches have reached their limits. ‘The research is an impressive example of visionary basic research with high clinical relevance,’ says Grüters-Kieslich.

Stainier and his team would like to use the research prize for a current project in which they are using special genetic tools to specifically produce different dystrophin decay variants.

A further aim is to transfer this method to other genetic diseases. If the concept proves successful, it could lead to new therapeutic approaches not only for Duchenne muscular dystrophy, but also for other rare diseases that have been difficult to treat to date.