Catherine Lubetzki

Professor of neurology at the Faculty of Health Sciences at Sorbonne University, Catherine Lubetzki has devoted her career to research into multiple sclerosis (MS) for more than 30 years. Her work has provided a better understanding of the mechanisms of this autoimmune disease which affects more than 100,000 people in France, and has opened the way to new therapeutic perspectives.

Born into a medical family, Catherine Lubetzki was drawn to neurology by chance. "We chose our internships in alphabetical order, according to our name," recalls the neurologist. "In my third year, the draw fell on the letter M. So I was the last in my class to be able to choose. Coming out of a difficult surgical internship, I reluctantly chose neurosurgery from the two remaining options." In the end, she discovered an exceptional department, both in human and professional terms, and made a seminal encounter. "The head of the department was a man of great quality and world-renowned for his stereotactic surgical treatment of abnormal movements. He used to take us to the operating room, where he operated to opera arias. It was extraordinary to see patients suddenly stop shaking during these neurosurgical treatments followed, years later, by deep brain stimulation methods", recounts the enthusiastic professor.

At the start of her residency, Catherine Lubetzki spent a year in Prof. Glowinski's neuropharmacology laboratory at the Collège de France. This was another key encounter that introduced her to neuroscience research. A few years later, she began to take an interest in multiple sclerosis, an autoimmune disease characterized by chronic inflammation of the nervous system, leading to the destruction of myelin, the protective sheath of nerve fibers. It causes motor, sensory and cognitive disorders that can progress to irreversible disability. "I was very touched by these young patients of my age who were given a diagnosis for which no treatment was available", confides the neurologist.

From the laboratory to the bedside

To understand this disease better, the clinician continued her research in the neurochemistry laboratory at the Pitié-Salpêtrière Hospital, starting a fruitful collaboration with Dr. Boris Zalc, a specialist in lipids of the nervous system. During her thesis under his supervision, she worked on oligodendrocytes, the central nervous system cells that synthesize myelin. She then completed a series of internships in various departments in the Île-De-France region, before becoming clinical director at the Pitié-Salpêtrière Hospital, working alongside renowned neurologists such as Olivier Lyon Caen and Yves Agid, founding members of the Institut du Cerveau (the Brain Institute).

In the 90s, she and her colleagues developed a model to study in vitro the phenomenon of myelination (the formation of a myelin sheath). To succeed, you need hard work and ideas, but also a certain amount of luck. "One evening, we left a Petri dish containing oligodendrocytes and other nerve cells in the oven. The next day, we noticed that the cells had a double contour very suggestive of myelin. We'd done it!"  With this easy-to-handle model, she explored many fundamental questions, demonstrating the axonal specificity of myelination and the key role of electrical activity. Since then, she has never ceased to combine research and clinical work. "We are fortunate at Pitié-Salpêtrière to be able to carry out both activities on the same site", a "luxury" according to the woman who was head of the neurology department and coordinator of the MS clinical research center for some ten years.

Catherine Lubetzki, who has been in charge of the medical-university neuroscience department at APHP-Sorbonne University since 2019, is the first woman to receive the prestigious Charcot Prize in 2019. Two years later, she was awarded the 7th Pasteur-Weizmann International Prize for her research into myelin regeneration in the treatment of this crippling disease.

A doctor on the move

Over the years, research into this pathology, which more frequently affects women, has made significant advances. Since the mid-1990s, the development of immunomodulatory and then immunosuppressive treatments has made it possible to control inflammation and prevent relapses in relapsing forms, which account for 85% of cases in the early stages of the disease. This breakthrough, which is still ongoing, has transformed the lives of thousands of patients. "We have observed a reduction of over 80% in new lesions, depending on the molecule. A real success story! But some patients, despite a well-managed treatment and an almost complete disappearance of relapses, continue to develop a slow and continuous worsening of their neurological symptoms. This is known as "silent" or "inflammation-independent" progression. What's more, in 15% of cases, multiple sclerosis develops progressively from the outset", explains the neurologist.

If the challenge of the 2000s was to treat relapses, the challenge of the 2020s is to prevent the progression of disability linked to neurodegeneration, by promoting myelin regeneration (remyelination) or neuroprotection. Numerous studies aimed at developing remyelinating treatments are underway worldwide. These include a therapeutic trial based on the neurologist's research. "In 1996, with Bruno Stankoff, a long-standing collaborator with whom I co-direct the current research team, we showed that if we blocked the electrical activity of neurons, we inhibited myelination, and vice versa. And after years of preclinical strategy, we have recently moved on to clinical translation. In partnership with the Quinze-Vingts hospital, we are conducting a therapeutic trial to assess the effect of stimulating electrical activity on remyelination, by sending electrical impulses into the optic nerve of MS patients who have recently had optic neuritis, which destroys the myelin of the optic nerve. The trial is well advanced and we hope to have the first results in less than a year," she says.

The neurologist is also keeping a close eye on other work being carried out in her laboratory, including a study to test molecules that promote myelination. "At the Brain Institute, we benefit from a strong link between clinical, fundamental and industrial research. We need industrial partners to conduct large-scale therapeutic trials," explains the clinician-researcher. Within 10 years, we hope to have treatments for the progressive form of MS available to patients.

Her team includes MS imaging specialists, neurobiologists, clinicians and clinical research experts, enabling multidisciplinary research. As far as imaging research is concerned - an essential tool for assessing treatment efficacy - "Fifteen years ago, Bruno Stankoff developed a method for quantifying the myelin content of lesions in patients' brains. This marker of efficacy is essential for monitoring demyelination or remyelination processes and testing new treatments", she explains.

Other studies aimed at understanding the causes of this multifactorial disease are being carried out at the Brain Institute. These include the role of environmental factors (such as endocrine disruptors), interactions between axons and immune cells in the central nervous system, and their impact on myelination and myelin repair.

Sharing

Vice president of the Sorbonne University Foundation since 2018, Catherine Lubetzki is currently Medical Director of the Brain Institute, a responsibility she carries out alongside her clinical work. To encourage clinician-researcher careers, she is convinced that it is essential to foster interactions: thus the Brain Institute has developed the STARE program, which offers medical students the opportunity to spend one or two weeks in one of the Institute's research teams. "The Déclic program, for its part, encourages researchers to meet clinicians and patients to better understand the diseases they are working on. We are also setting up programs for paramedics and have just launched Institut du Cerveau-APHP interface contracts, which offer young clinicians the chance to devote themselves to research for 3 years."

Bringing research and clinical practice closer together is, according to the neurologist, one way of developing disruptive innovations. "It's important to be able to take a step aside from the beaten track, but also to stay up to date technologically. Artificial intelligence, for example, enables us to use the data available to the scientific community to ask new questions without having to repeat experiments," she points out.

A role model for medical students, Catherine Lubetzki is more broadly an example for all those who wish to combine cutting-edge research, clinical activity and high-level responsibility.