Pascale Bomont: Committed to Rare Diseases

An expert in rare neurodegenerative diseases, Pascale Bomont has obtained European funding enabling her to boost her research. Research that aims to elucidate the role of the cytoskeleton in a healthy or diseased nervous system. This could lead to the development of treatments for a wide range of diseases related to disorders of this internal cellular scaffold – from the rarest to the most common.

Pascale Bomont

Boxes, files, aquariums... Inserm researcher Pascale Bomont's move was no picnic. She has recently joined Institut Neuromyogène* in Lyon, a center dedicated to studying the pathophysiology of the nervous system and muscles. It is there that she has decided to conduct a project supported by an ERC Consolidator Grant of €1.8 million, aimed at exploring the role and modes of regulation of the nervous system cell cytoskeletons, and more particularly those of its component neurofilaments.

The cytoskeleton is the internal scaffolding of our cells: it gives them their form and the ability to resist mechanical constraints. By elucidating the as yet unknown functional roles of the neurofilaments that are part of its composition within the neuron, Bomont will be able to better understand the pathological mechanisms involved in certain diseases. The stakes are high. "Most neurodegenerative diseases, whether rare or common, present early cytoskeletal abnormalities with the formation of neurofilament aggregates, she explains. In several diseases, genetic manipulations have shown that removing these aggregates resolves the symptoms in mice. If we are to devise a treatment for use in humans, we must identify and target the regulators of those neurofilaments".

To reach her goal, Bomont started from scratch – or thereabouts: "None of the animal models were suitable, so I created new ones in the zebrafish. We can now use them to study the dynamics of the cytoskeleton, for a better understanding of how it works. At the same time, we will reproduce in the fish mutations associated with rare diseases, in order to study the cytoskeletal abnormalities they generate, distinguish their roles in neuron death and develop new therapeutic approaches,” explains the researcher.

Twenty years of research into rare diseases

For Bomont, rare diseases are a source of inspiration and motivation: she defends the right of every patient to equal treatment and the importance of studying rare diseases to enrich our knowledge of the living world. And this is a subject she knows well, having devoted 20 years of her career to various rare neuropathies, including giant axonal neuropathy (GAN) – a fatal neurodegenerative disease that strikes the central and peripheral nervous system from an early age. She has been interested in this field since her Ph.D. in human genetics, which she prepared at the Institute of Genetics and Molecular and Cellular Biology (IGBMC) in Strasbourg. Back then, in the early 2000s, the human genome was not yet fully sequenced: identifying the genes responsible for rare diseases was a feat of ingenuity for Bomont. This research also led her to meet the families of patients, marking a turning point in her approach to it: "While understanding the fundamental mechanisms deregulated in the diseases is crucial, transforming this into innovation to help patients is a matter of urgency and an ongoing motivation in my work", she testifies.

Her doctorate in hand, she flew to San Diego in the United States to join a laboratory at the Ludwig Institute for Cancer Research, expert in the study of the cytoskeleton and neurodegenerative diseases. There she immersed herself in the field of cell biology in order to apply it to her GAN model. Armed with her advances, Bomont then developed her neurobiology expertise, obtaining in 2007 a role of research fellow at Inserm, whereupon she returned to France to join the Mediterranean Neurobiology Institute in Marseille. Thanks to AFM-Telethon funding, she set up an emerging team and developed new models to study this neuropathy, using skin biopsies from patients and mice. In 2011, the ATIP-Avenir program enabled her to create her research team at the Institute for Neurosciences of Montpellier. Deploying her expertise in genetics, cell biology and neurobiology, she identified new genes for rare diseases and developed diagnostic tools and fish models. As such, she discovered several GAN pathophysiological mechanisms, whose repercussions go far beyond this rare disease: the pathways identified, fundamental in the biology of the neuron, are in fact impacted in dozens of diseases, including cancer and muscle diseases.

In her current role of Inserm Research Director in charge of the Mechanisms and therapies for neuromuscular diseases team at Institut Neuromyogène in Lyon, Bomont continues her fight for rare diseases. In addition to European funding for her project on the role of the cytoskeleton in the nervous system, she has obtained AFM-Telethon support for a project on GAN therapies.

Energy, inventiveness, solidarity

Bomont owes her exemplary career to a good dose of energy and inventiveness, which lead her to explore every avenue likely to lead to a discovery or new treatment. "I use all means possible in my quest to provide answers: our work is creative! Where necessary, I call on experts from other disciplines." She is also keen to share her knowledge: Fête de la science, Semaine du cerveau, Téléthon, any event or occasion is an opportunity to open the doors of her laboratory to the patients’ families and general public, propose practical exercises or create scientific videos. Her strength is also her team: "We are more than the sum of our respective areas of expertise, working in synergy to get the best from each of us and grow our efforts, creativity and resources, with the pleasure of advancing together". There is no doubt that research into rare diseases has found itself a committed ambassador.

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*Unit 1217 Inserm/Université de Lyon