Joint Transnational Call 2014 (JTC2014)


Multiple system atrophy is a fatal disorder with severe motor impairment and dysautonomia affecting over 30,000 people in Europe. Accumulation of α-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 α-synuclein in oligodendrocytes. This project aims at counteracting disease progression by targeting key mechanisms contributing to α-synuclein accumulation. Using complementary in-vitro and in-vivo models, we will test the efficacy of: 1) increasing α-synuclein clearance by activating autophagy with rapamycin 2) reducing seeding of aggregation by preventing its cleavage with VX-765 3) reducing α-synuclein aggregation using the oligomer inhibitor anle138b and 4) preventing α-synuclein propagation via 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 α-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.

  • Meissner, Wassilos (Coordinator)
    University of Bordeaux [FRANCE]
  • Giese, Armin
    Ludwig-Maximilians-University Munich [GERMANY]
  • Wenning, Gregor
    Innsbruck Medical University [AUSTRIA]
  • Galabova, Gergana
    Affiris AG [AUSTRIA]
  • Griesinger, Christian