Research

A team led by Professor Jeanne Amiel from the Necker Hospital in Paris was the first to identify the genetic origin of CCHS. Thanks to this discovery by the French scientists, we now know that the disease is induced by mutations within the PHOX2B gene encoding a transcription factor, that is a protein responsible for regulating other genes. A team led by Professor Jean-François Brunet of the Institute of Biology at Ecole Normale Supérieure in Paris, using tests on mice, has developed the first model to assist in understanding the cellular and molecular mechanisms involved in the disease and to test potential drugs.

Currently in France, nearly 30 scientists from renowned institutions, such as the Institute of Genetic Diseases, the Necker Hospital in Paris, Marseille Medical Genetics, Paris Descartes University, the Aquitaine Institute for Cognitive and Integrative Neuroscience in Bordeaux and Sorbonne University Laboratory, La Pitié Salpêtrière Hospital in Paris, Inserm (French National Institute of Health and Medical Research) at Robert Debré Hospital in Paris, are engaged in the efforts to decode the disease, understand its mechanisms and select a candidate drug molecule.

Among other things, the researchers are working to develop cellular and computer-based models to identify the signalling pathways involved in CCHS and the molecules that activate these pathways. There are also studies on cells and stem cell lines harvested from patients and electrophysiological studies on brain stems in mice. The ultimate goal of the research is to develop an effective drug therapy – medication to treat Ondine’s curse.

This work is coordinated by a start-up called AtmosR, founded in 2019 by patient families and researchers convinced that in a few years’ time, a therapeutic solution could be provided to patients so that they can become independent of mechanical ventilation by to restoring the basic respiratory rhythm and eliminating the significant risk associated with the lack of natural chemoreflexes.

The AtmosR start-up plans to address all phases of the drug development chain, such as:

•  Identification and selection of a candidate drug molecule through ongoing pre-clinical work;
• Phase 1, 2 and 3 clinical trials;
• Work on refining the drug molecule – developing dosage, routes of administration;
• Discussions with regulatory agencies – the FDA in the USA and EMA in Europe – with a view to obtaining an ODD marketing authorisation (i.e. so-called orphan drug designation for treating a rare disease).