Multiple Sclerosis is a chronic autoimmune disease. The symptoms of the disease are motor disorders, sensory disturbances, balance disorders, visual disturbances…
Multiple Sclerosis is a disease of the central nervous system in which the immune system, which is usually involved in the fight against viruses and bacteria, attacks the individual’s own specific elements. The inflammatory response of multiple Sclerosis destroys the protective myelin sheath surrounding neuron extensions, called axons.
MS affects about 1 person in 1000, nearly 70 000 people in total. The disease appears at an average age of 30. Most of the time, the disease is manifested by successive outbreaks in 85% of cases, but Multiple Sclerosis can also develop gradually without any outbreak (15%). The development of a disability due to the disease is inevitable, which, after 30 years, forces the patient to move around in a wheelchair.
Institut du Cerveau – ICM RESPONSES
TOPICS AND RESEARCH TEAMS
- Decipher the mechanisms involved in the destruction of the nervous system to better fight the disease with Bertrand Fontaine’s team.
- Understand necessary mechanisms for myelin repair to identify therapeutic targets with Catherine Lubetzki and Bruno Stankoff, Brahim Nait Oumesmar and Anne Baron Van Evercooren’s teams.
- Develop powerful and complementary tools to identify reparative molecules in a very large number of tested molecules, with Jean-Léon Thomas, Brahim Nait Oumesmar and Anne Baron Van Evercooren’s teams.
- Repair damage by supporting spontaneous remyelination, or through stem cells with Catherine Lubetzki and Bruno Stankoff, Brahim Nait Oumesmar and Anne Baron Van Evercooren’s teams.
- Assess the evolution of the disease through cutting-edge techniques to predict patients’ evolution and adapt treatments with Catherine Lubetzki and Bruno Stankoff, and Bertrand Fontaine’s teams.
Genes modulating MS risk
Bertrand Fontaine and Sophie Nicole’s team took part, within an international consortium, in different studies carried out on more than 17 000 patients, which enabled to identify genetic risk factors involved in MS, and several protective genes. Affected genes are involved in the recognition of foreign elements by the body. The identification of mutations or combinations of mutations modulating genetic risk enables us to better understand the onset of the disease and consider therapeutic solutions. A clinical study in patients with MS and targeted according to their genetic ground, is currently ongoing at the Therapeutic Assessment Center.
Restorative molecule screening tools
In the context of the NeurATRIS consortium, Brahim Nait Oumesmar has developed a high-throughput molecule screening in-vitro test supporting oligodendrocyte precursor cell differentiation in mature oligodendrocytes, which role is myelin repair. Identified candidate molecules are tested in vivo in an original model developed by Bernard Zalc. He has generated a transgenic Xenopus, an amphibian which myelin is very close to humans’ and in which it is possible to induce demyelination. Through Xenopus tadpole transparency, it is possible to visually follow remyelination, and so test candidate molecule remedial power.
Repair damaged myelin through skin cells
Turn skin cells into nerve cells to repair the damage caused by multiple sclerosis and some leukodystrophies, is the challenge taken up by Brahim Nait Oumesmar and Anne Baron Van Evercooren’s team. These extremely encouraging results would enable the consideration of a cell therapy from the affected patients’ own cells. This team has also highlighted that human neural stem cells have a double therapeutic effect : anti-inflammatory and promyelinating.
Myelin repairing factor
Brahim Nait Oumesmar and Anne Baron Van Evercooren’s team has highlighted the beneficial role of a molecule, named Olig2, in myelin repair. Its overexpression stimulates oligodendrocyte regeneration, these cells are responsible for myelin production. This discovery could have implications on the development of therapeutic strategies aiming at stimulating MS damage recovery.
Rescuing progenitor cells ?
The central nervous system contains a large population of oligodendrocyte precursor cells or OPCs. These cells are responsible for the production of new oligodendrocytes which role is to make and repair myelin sheath. Catherine Lubetzki and Bruno Stankoff’s team has showed, in an experimental model, that during demyelination, oligodendrocyte precursor cells are activated and express inflammatory factors (Ccl2, and IL1b) which support their migration and differentiation into oligodendrocytes in the demyelinated area. Identification of the mechanisms governing remyelination is the first step towards the development of therapies for MS patients.
Estimate the evolution of multiple sclerosis through a cutting-edge technique
Thanks to an innovative program of multi-modal imaging in tomography by positron emission (PET SCAN), Bruno Stankoff and Catherine Lubetzki’s team was able to visualize demyelination and remyelination of neurons. This method could be used to identify patients according to their ability to renew destroyed myelin, and thus guide therapeutic management. Using a different tracer (flumazenil) in PET SCAN, researchers were able to quantify neuronal degeneration and trace it in MS patients.
Identify biomarkers of the disease
Bruno Stankoff is the coordinator of a study aiming at discovering differential biomarkers of inflammation, myelin destruction and neurodegeneration through advanced imaging techniques. The identification of biomarkers will help predict disease progression and patient response and thus guide their therapeutic management.
A treatment against primary progressive forms
The Oratorio protocol in partnership with Roche and coordinated by Caroline Papeix has tested the effectiveness of Ocrelizumab in patients with MS primary progressive forms. The extremely encouraging results of this phase III study show that this drug significantly limits the progression of the disability in patients, with a 24 % decrease of the risk of disability aggravation.
A treatment improving patients’ health status
For the first time, a drug developed by MEDDAY, MD1003, slows disease progression and improves the health status of patients with progressive multiple sclerosis. The drug should be available on the market in the short term, which is extremely encouraging for both clinicians and patients.