Trek1/trek2 as targets for the treatment of migraine

Inventors have found that the MT mutation puts an alternative start codon in frame which leads to the translation of a second TRESK fragment. Surprisingly, the 2 gene products, termed MT1 and MT2, have differential dominant negative effects: MT1 targets TRESK while MT2 targets TREK1 and TREK2, members of another subfamily of K2P channels. Furthermore, they have shown that by co-assembling with and inhibiting TREK1 and TREK2, MT2 increases TG excitability. This resolves the contradictory lack of effects of TRESKC110R which targets only TRESK and not TREK1 or TREK2. Together their results demonstrate that alternative translation initiation is a mechanism initiated by the TRESK-MT mutation which leads to two protein fragments with dominant negative effects on distinct channel targets. The present invention relates to a method for treating migraine in a subject in need thereof comprising a step of administering the subject with a therapeutically effective amount of agonists of: TREK1, TREK2, TRESK-TREK1, TRESK-TREK2 or TREK1-TREK2.

Keywords: Pain - Migraine - Repositionning
Patent Application number: EP17305813.2
Perrine ROYALGuillaume SANDOZ
Neuron. 2018 Dec 12. pii: S0896-6273(18)31048-1. doi: 10.1016/j.neuron.2018.11.039



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Patent filling date: 29-07-2017
Second indication: Yes

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