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Fighting Anxiety with Importin-based Therapeutics

Periodic Reporting for period 1 - FAITh (Fighting Anxiety with Importin-based Therapeutics)

Reporting period: 2017-11-01 to 2019-04-30

Anxiety and stress-related conditions represent a significant health burden in modern society. Anxiety disorders are currently treated with a variety of agents targeting synaptic mechanisms. These agents either directly affect neurotransmitter receptor systems or modulate neurotransmitter levels or availability, but their long-term use is limited by problematic side effects and suboptimal efficacy. The development of new anxiolytic drugs has been fraught with difficulty, hence there is a need for new targets and new avenues for therapeutic development.
Importin-dependent transport mechanisms link synapse to nucleus in a diversity of physiological contexts, rendering them potentially interesting targets for behavioural control. However importins and related molecules have not been evaluated for roles in anxiolysis in the past. During
the course of comprehensive phenotyping of importin mouse mutants we discovered that importin alpha5 knockout mice present strongly reduced anxiety levels. During the course of this project we validated the role of importin alpha5 in the regulation of anxiety, and characterized approved drugs affecting this pathway that can be repositioned for anxiety treatment. We have filed for IP protection on these discoveries and are currently seeking pharma partners for further development towards cinical utilization.
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