Existing treatments for multiple sclerosis generally focus on the ability to slow the progression of the disease. However, the incomplete understanding of the mechanisms of pathology hampers their effectiveness and limits treatment options. A study conducted at the University of Alberta (Canada) is one of the few to explore a neuroregenerative therapy strategy, using in particular a molecule called fractalkine. In sick mice, the latter would have reversed the demyelination process, by renewing the myelin-producing cells. This remyelination makes it possible in particular to restore the fluidity of the neuronal connection. The molecule might thus potentially be used to treat other neurodegenerative diseases.
Most often manifested by mild symptoms (at the beginning), multiple sclerosis is a demyelinating autoimmune disease that sometimes goes so far as to completely paralyze patients. Gradually destroyed by the inflammation caused by the disease, the myelin sheath of neurons is no longer able to properly support communication between nerve fibers. In other words, the disappearance of this sheath hinders the fluidity of the circulation of nerve information.
On the other hand, you should know that the regeneration of oligodendrocytes, the only brain cells that can produce myelin, is particularly inefficient in humans. These specific cells are differentiated from neural stem cells present in the brain. The aim of the new study, published in the journal Stem Cell Reportsis to confirm a strategy to stimulate these neural stem cells to promote remyelination by the generated oligodendrocytes.
« We’ve made a lot of progress in the medical and research communities on MS progression-modifying therapies, but what we really don’t have — an unmet need in the MS community —, these are regenerative therapies for the nervous system », Explain Anastassia Voronova, assistant professor in the Department of Medical Genetics at the University of Alberta, and co-lead author of the new study.
In a previous study, Voronova indeed demonstrated that fractalkine (or chemokine CX3CL1) might stimulate the differentiation of neural stem cells into oligodendrocytes. It was previously thought that this molecule only had a role in the immune system, in particular the modulation of neuroinflammation. But Voronova’s research has shown that it may play a role in the process of remyelination. ” The molecule and its receptor work together to trigger a signaling cascade inside neural cells “, she explained in a communiqué.
The major role of fractalkine in remyelination is now confirmed in mice (as part of the new study). ” If we can replace these lost or damaged oligodendrocytes, they might produce myelin, and this is thought to stop the progression of the disease, and even reverse some of the symptoms. », Estimates the expert.
A molecule tested on healthy and sick mice
As part of their research, the Canadian scientists administered fractalkine to mice in which they had chemically induced a disease mimicking multiple sclerosis. The treatment was then found to increase the number of new oligodendrocytes, as well as reactivated progenitor cells, in diseased mice. Remyelination would have occurred both in the corpus callosum and in the cortical gray matter. A reduction in neuroinflammation was also observed.
Namely that during the study, the researchers previously tested the safety of the treatment on healthy mice, and observed similar effects (production of new oligodendrocytes). The next step was to determine how the molecule would act on mice where the disease was induced, with the ultimate goal of clinical trials.
Furthermore, the researchers also demonstrated that the activated oligodendrocytes in vitro and microglia (macrophages found in the central nervous system) express the specific fractalkine receptor. This activation of the receptors demonstrates the pro-regenerative role of fractalkine, both in a diseased mouse model and at the level of isolated cell cultures.
As a next step, the researchers plan to test the molecule on other neurodegenerative diseases (on mice) involving demyelination. The route of administration of the new treatment will also be studied, in order to overcome the famous problem of the blood-brain barrier. The Voronova team will notably explore the route of administration by nasal spray, the effectiveness of which seems promising according to other studies.
