Several weeks ago we introduced you to the research project by Cédric Raoul, researcher at UMR901 Inserm at INMED, Marseille. This project was funded in the first call for projects by the Thierry Latran Foundation.

Recently, Cédric Raoul (photo) in conjunction with several teams based in Marseille, Paris and Uruguay, published work which revealed a new toxicity mechanism involving the astrocytes and affecting motor neurons.

The astrocytes present in ALS function abnormally leading to motor neuron damage and degeneration. Indeed, the cells of the human body naturally exchange information via small molecules called cytokines.

In ALS, we know that the astrocytes “communicate” information to the motor neurons via toxic factors. However, these factors and the precise mechanisms involved have never been completely understood. With the work from the teams coordinated by Cédric Raoul, we now understand the neurotoxic role of two cytokines: interferon-gamma (or IFN-γ) and the LIGHT molecule.

IFN-γ produced by the astrocytes activates the LIGHT molecule and a sequence of events leading to the destruction of motor neurons. By blocking this sequence of events in the ALS experimental models the researchers have succeeded in slowing the degeneration of motor neurons and extending life expectancy in these models.

IFN-γ and LIGHT therefore have become two potential targets for development of future treatment approaches for ALS. The road ahead for this treatment development remains long but Cédric Raoul’s laboratory is already exploring gene therapy and immunotherapy models which aim to inactivate IFN-γ and LIGHT.

Different representations of the IFN-γ molecule (source : findtarget.com)

The Thierry Latran Foundation is supporting the development of these therapeutic models as part of the project focused on innovative gene therapy to deliver molecular inhibitors of neuronal death pathways to the spinal cord and brain motor neurons in ALS mice models.

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Source : Cell Death and Differentiation : IFNγ triggers a LIGHT-dependent selective death of motoneurons contributing to the non-cell-autonomous effects of mutant SOD1.

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