CE17 - Recherche translationnelle en santé

Development of an innovative therapeutic molecule for a rare disease: ALS – Neurovita-SLA

Submission summary

The objective of the research project "Neurovita-ALS" is to study the therapeutic potential of a new molecule, Neurovita, in the treatment of amyotrophic lateral sclerosis (ALS). It brings together, in a translational approach, two academic laboratories, Institut Pasteur (IP) and Institut du Cerveau (ICM), and a French biotechnology company, Neurophoenix.

ALS is a neurodegenerative disease that gradually destroys the motor neurons inducing progressive muscle paralysis and that quickly becomes lethal when the respiratory muscles are affected. The disease appears around the age of 60. The life expectancy of patients is very short: the median survival is less than three years from the onset of symptoms. In France, this pathology currently affects 5 to 7,000 patients with an annual incidence close to 2.5 per 100,000 inhabitants. Currently available treatments are limited to two molecules: Riluzole and Edaravone, which only extend patients' lives by a few months. In this context, new molecules are actively researched and several clinical trials following new therapeutic approaches are currently underway.

The causes of the disease remain unclear. In one in ten cases, a genetic origin is proven. In all other cases a combination of genetic and environmental factors would be the cause. Whatever the origin of the disease, it begins with the dysfunction and atrophy of the motor neurons (located in the cerebral cortex and in the spinal cord) which control muscle activity. Later, an inflammatory mechanism involving the patient's immune system aggravates the pathology. The inflammatory component of the disease is linked to the activation of pro-inflammatory lymphocytes of type Th1 and Th17 and to the disappearance of the subpopulation of lymphocytes called regulatory T cells, or Tregs, whose function is to inhibit them.

A molecule, which could both stimulate the survival of motor neurons, slow their atrophy and at the same time inhibit neuro-inflammation - for example by restoring the activity of Tregs - would delay the onset of lethal paralysis and prolong the life of patients. By treating the symptoms common to all forms of ALS and not the cause, this molecule could be applied to all patients.

One such neuroprotective and anti-inflammatory molecule, Neurovita, derived from the rabies virus, was isolated at IP and is now developed by Neurophoenix for the treatment of optic neuropathies.

The ambition of our project is to establish by a double in vitro and in vivo approach that a treatment with Neurovita:

• promotes the survival of motor neurons derived from patients suffering from ALS and in an ALS mouse model
• inhibits a deleterious inflammatory response and reconstitutes the population of Tregs in an ALS mouse model
• functions as a powerful disease modifying drug candidate for ALS in a preclinical mouse model by targeting the two arms of disease (MNs death and Tregs exhaustion)
• is more efficient than other disease modifying drug candidate which targets only one arm of the disease

Recognized expertise, accumulated experience (> 20 years) and the very strong complementarity of the three partners maximize the chances that this project will lead to the launch of a clinical trial.

Project coordination

Monique LAFON (INSTITUT PASTEUR)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Neurophoenix NEUROPHOENIX
IP INSTITUT PASTEUR
ICM ICM

Help of the ANR 652,533 euros
Beginning and duration of the scientific project: January 2021 - 36 Months

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