Inaugural lecture Paul Ehrlich Chair - Rare genetic diseases: a unique window into biology
How the study of rare genetic diseases sheds light on biology and vice versa: the emblematic example of ciliopathies
By Hélène Dollfus, USIAS Paul Ehrlich Chair 2024-2026
With an introduction by Jean-Louis Mandel, IGBMC, USIAS Chair of Human Genetics
By definition, any rare disease affects only a small number of individuals; yet, with more than 6000 types of rare disease in existence, the total burden worldwide is significant. Their prevalence is estimated to be 3.5–5.9% of the world's population, or 263–446 million people globally at any point in time.
Around 80% of rare diseases have a genetic cause, almost 70% of which present in childhood; about 95% lack approved treatments. They are often chronic, progressive, and debilitating, and can lead to significant morbidity and mortality.
Not only do rare genetic diseases represent a serious global public health issue, they also represent an exceptional field of research, conducive to scientific discovery, because they combine so many facets of medicine.
Recent years have seen major advances, with giant steps forward thanks to, for example, the ability to decrypt (read) a patient’s entire genome in order to identify the mutation responsible for the disease. In addition, new biotechnological tools make it possible to dissect the mechanisms of the many biological causes responsible. This has led to the development of, and access to, long-awaited treatments such as gene therapy, and compounds that act directly on genes and their products. However, these giant strides are still limited to certain diseases, and also raise ethical and medico-economic questions which concern society as a whole.
This lecture will offer a window into the research on rare genetic diseases by looking at the history of one group of such diseases: ciliopathies. The focus will be on the central role in biology and medicine of the cilium, an organelle that has been known for a long time, but whose importance has only recently become clear, when it was found to be responsible for many diseases often affecting several organs.
Progress in genome sequencing has made it possible to identify many of the genes responsible for ciliopathies, but has also revealed a very broad clinical spectrum, providing an example of phenotypic variability. In vitro and in vivo modelling of these diseases is being used to understand why and how dysfunction of this antenna affects various organs, and to search for possible entries for treatment.
The case of ciliopathies will illustrate how research on rare genetic diseases can offer unique opportunities to increase our fundamental understanding of the complex genetic processes underlying human health, but also how this knowledge can help develop treatments and address an important global health problem. Therapeutic advances for rare genetic diseases are underway with numerous approaches, some of which are already in therapeutic trials or even on the market. The lecture will show that we are entering a truly unprecedented era of health care.
This is the inaugural lecture of the Paul Ehrlich Chair at USIAS. It is intended for a broad audience, who will be invited to learn about the subject from a pioneering researcher working at the forefront of research. The lecture will be held in English.
The lecture is the first part of a larger event, which starts with the inaugural lecture of the Marc Bloch Chair, "The precision of poetry and the imagination of science", by Monica Manolescu (in French) - see the full programme of the afternoon. It is possible to attend a single lecture or both lectures.
---
The Paul Ehrlich Chair in the life sciences was created in 2022, as one of three associated chair positions with a duration of two years, for Strasbourg-based researchers who have made an exceptional contribution to their field. The Chair is named in honour of Paul Ehrlich (1854-1915), a German physician and scientist who studied in Strasbourg and is widely recognized for his research on haematology, immunology and pharmacology. Known as the father of chemotherapy, he was awarded the 1908 Nobel Prize in Physiology or Medicine for his contributions to immunology.
---
Image credit: DNA image: Grumpy Beere, Pixabay; Paul Ehrlich: Harris & Ewing, US Library of Congress
