When a genetically predisposed individual is exposed to a specific environmental factor or factors, an abnormal inflammatory response known as an autoimmune response is triggered by activation of myelin-autoreactive immune cells.
These inflammatory phases that make up the flare-ups of multiple sclerosis continue until persistent and chronic inflammation sets in, initiating a cell cascade that causes neuron degeneration and permanent disability.
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that affects the brain, spinal cord and optic nerves, and whose symptoms result from a decrease or even disappearance of communication between certain regions of the brain and spinal cords and peripheral organs.
The nervous system
Through millions of receptors, the nervous system receives sensory information (from the skin, muscles, sense organs), via sensory neurons, about changes (stimuli) coming from the internal environment (the body) or the external environment (the environment). The central nervous system (brain and spinal cord) integrates (processes, analyses, and interprets) the information it receives: it perceives the nature of the information (source, intensity) compares it with reference values and decides on an appropriate response. The central nervous system responds to integration by ordering motor activity (control), via motor neurons, such as muscle contraction. The central nervous system controls and receives information from other organs of the body via the autonomic or vegetative system over which we have no conscious control, such as the heartbeat.
Neurons
Neurons are the cells that allow the transmission of information between the central nervous system and the periphery. They consist of a cell body, an axon and terminal extensions. Axons have the ability to transmit and receive electrical signals (nerve impulses) that are the means of sensory and motor communication.
Neuron axons are protected and nourished by a lipid sheath called myelin, which acts as insulation around electrical wires. Myelin also acts as an accelerator of nerve impulses. Myelin is the white substance of the brain.
Multiple Sclerosis Injuries
The lesions or “plaques” observed in the brain or spinal cord of magnetic resonance imaging (MRI) patients are characterized by four components:
- Inflammation: Inflammation is a defense response of the body to external aggression mediated by immune cells. In MS, the immune response is directed against the body itself, called an autoimmune disease. Immune cells attack a component of the CNS: myelin
- Demyelination: Microscopic observation of a lesion of multiple sclerosis. Neurons (cell body and axon) are labelled green, myelin is labelled red.
The protective sheath is lost on some axon segments.
- Neuronal degeneration: Without their protective sheath, neurons degenerate and die. On this microscopic observation, the red-labelled myelin completely disappeared. The axons retracted and the cell bodies began to die. It is called neuropathy.
- Repairing Myelin: In some lesions, there is a spontaneous phenomenon of myelin repair which, if it occurs at an early stage after the lesion has formed, prevents neurons from dying and disability from developing.
This is not uncommon, but there is considerable heterogeneity among patients regarding this intrinsic ability to repair damage caused by multiple sclerosis disease. The nerve influx disappears in the affected brain areas. Information no longer circulates; symptoms appear.
At Paris Brain Institute
- A study conducted by Beatriz Garcia-Diaz and Anne Baron Van Evercooren (DRE INSERM) at Paris Brain Institute. In the team of Brahim NAIT-OUMESMAR and Violetta ZUJOVIC has just highlighted the mechanism that allows the migration of Schwann cells, cells that repair the myelin sheath of peripheral neurons, into the spinal cord.
- Catherine LUBETZKI and Bruno STANKOFF’s team are also carrying out projects on demyelination and demyelination mechanisms.
- A collaborative study between the two teams led by Céline LOUAPRE and Violetta ZUJOVIC aims to develop a tool for the early assessment of disability progression in order to offer personalized and effective treatment to patients at the beginning of their illness.
About Inflammation
- Several studies by Professor Bruno Stankoff’s team, “Remyelination in Multiple Sclerosis: From Biology to Clinical Translation”, have revealed new mechanisms of brain inflammation in multiple sclerosis, thanks to new imaging tools based on the combination of magnetic resonance imaging (MRI) and positron emission tomography (PET).
- A collaboration between Violetta ZUJOVIC and Fabrizio DE VICO FALLANI has led to the identification of "key" genes that control the "pro-inflammatory" state of macrophages in multiple sclerosis."
About remyelination
- In an article published in the European Journal of Neurology, Vito Ricigliano, Benedetta Bodini and their collaborators at the Brain Institute demonstrate the protective effect of myelin repair on tissues surrounding lesions in patients with multiple sclerosis. This discovery highlights the potential for new therapeutic strategies and provides new insights for evaluating the efficacy of investigational remyelinating drugs.
- As part of an international consortium, Anne BARON-VAN EVERCOOREN and her colleagues have shown that the defect in remyelination in some patients with relapsing-remitting multiple sclerosis is not linked to an intrinsic defect in the oligodendrocytes, the myelinating cells of the brain, but to the toxic and inflammatory environment of the lesions.
- A study by the “Myelin Plasticity and Regeneration” team, co-led by Brahim NAIT-OUMESMAR, identified new inhibitors of the protein kallikrein 6 (KLK6) and demonstrated their ability to stimulate myelin production in experimental models.
