E-Rare - Appel à projets transnational pour la recherche sur les maladies rares dans le cadre de l’ERA-NET E-Rare-2

Targeting Alpha-Synuclein for Treating Multiple System Atrophy – ARTEMIS

Submission summary

Multiple system atrophy is a fatal disorder with severe motor impairment and dysautonomia affecting over 30,000 people in Europe. Accumulation of a-synuclein in oligodendrocytes plays a pivotal role, leading to glial and neuronal dysfunction and degeneration. These features are recapitulated in the PLP-SYN mouse model expressing a-synuclein in oligodendrocytes. This project aims at counteracting disease progression by targeting key mechanisms contributing to a-synuclein accumulation. Using complementary in-vitro and in-vivo models, we will test the efficacy of: 1) increasing a-synuclein clearance by activating autophagy with rapamycin, 2) reducing seeding of aggregation by preventing its cleavage with VX-765, 3) reducing a-synuclein aggregation using the oligomer inhibitor anle138b, and 4) preventing a-synuclein propagation via active and passive immunotherapy using AFFITOPE®. Finally, we will test the combination of the most promising strategies to obtain synergistic therapeutic effect. Efficacy readouts will include oxidative stress, unfolded protein response (in-vitro), cell survival, monomeric, oligomeric and post-translational modifications of a-synuclein (in-vitro and in-vivo), astroglial and microglial activation, as well as motor deficits (in-vivo). This project involves academic partners with strong expertise in multiple system atrophy and industrial partners with innovative therapeutic candidates. This unique combination at the European level will allow a rapid translation of successful strategies into clinical trials.

Project coordination

Wassilios MEISSNER (Institut des Maladies Neurodégénératives, Centre de référence maladies rares AMS)

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

UNIVERSITE DE BORDEAUX Institut des Maladies Neurodégénératives, Centre de référence maladies rares AMS
Affiris AG Affiris AG
MODAG GmbH MODAG GmbH
Innsbruck Medical University Department of Neurology, Division of Neurobiology
Ludwig-Maximilians-University Munich Zentrum für Neuropathologie und Prionforschung

Help of the ANR 234,000 euros
Beginning and duration of the scientific project: February 2015 - 36 Months

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