Paris brain institute develops new model for multiple sclerosis to better target molecules for treatment

Researchers at the Paris Brain Institute, led by Bernard Zalc, have developed a new model for multiple sclerosis (MS) that may help identify promising drugs for remyelination and halting the progression of the disease. MS is caused by the immune system attacking the brain and spinal cord, resulting in the loss of myelin, a protective sheath that surrounds nerve fibers and ensures proper nerve impulse conduction.

While progress has been made in controlling the inflammatory component of MS, neurodegeneration remains a challenge, and current treatments fail to stop the disease’s progression. Restorative treatments aimed at repairing myelin sheath lesions have proven difficult, and clinical trials of promising candidate molecules have been disappointing.

According to Zalc, current preclinical evaluation methods that rely on tissue observation of myelin-producing cells are insufficient for determining the effectiveness of candidate drugs. To be effective, drugs must also improve or restore motor and sensory abilities, making it challenging to connect specific demyelinating lesions to sensorimotor deficits.

The new model developed by Zalc and his team may help address this challenge by correlating myelin degeneration or regeneration with cognitive and motor abilities. With this approach, researchers can better identify and target molecules that may promote remyelination and halt disease progression.

A bridge between lesions and behavior

A team of researchers led by Catherine Lubetzki and Bruno Stankoff from the Paris Brain Institute have devised a new method to address a gap in their understanding. They utilized genetically modified Xenopus tadpoles, which have transparent bodies during their developmental stage, to count the number of oligodendrocytes responsible for myelin production in the optic nerve. This was then correlated with the animal’s motor and behavioral abilities.

To induce demyelination or remyelination, a process that indicates changes in the number of oligodendrocytes, the team introduced metronidazole into the tadpole’s aquarium. This substance was able to cause the loss of oligodendrocytes in the optic nerve, which resulted in impaired visual abilities observed through a virtual target avoidance test.

Researchers observed a spontaneous repair of myelin, measured by an increase in the number of oligodendrocytes and improvement in visual test results, after the tadpoles were exposed to metronidazole. They also found that molecules promoting remyelination could accelerate this phenomenon.

According to Zalc, the variation in motor and sensory performance of the tadpoles was directly correlated with the level of demyelination and tissue remyelination. Therefore, this model can serve as a valuable tool for testing the remyelination potential of new drugs, which can save time and money by avoiding long and costly clinical trials.

There is an urgent need for molecules that can act on demyelination because it can lead to irreversible axon damage and neuronal death, resulting in the progression of disability.

This new tool provides a way to monitor and advance our understanding of the link between visual disorders, which is a common symptom of multiple sclerosis, and associated demyelination lesions. Zalc concludes that this is a significant step towards future therapeutic success.

Source: Paris Brain Institute

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