NRU part of large Lundbeck Foundation collaborative project grant
- Published: Monday, 16 January 2023 15:02
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The total project grant is worth 39 mio DKK, and NRU will get funding for 5 years of post doc salary and running costs for pig PET studies and other project-related costs, totalling ~6 mio DKK.
Abstract: Serotonergic psychedelics, such as LSD and psilocin, have emerged as promising drug candidates for treatment of brain disorders, such as depression. We have discovered that these psychedelics also bind with high-affinity to a novel allosteric site in the brain-derived neurotrophic factor (BDNF) receptor TrkB and act as positive allosteric modulators (PAMs). We hypothesize that the neuroplasticity-promoting and antidepressant effects of psychedelics may be mediated via TrkB, and that the psychedelic effects arising from their 5-HT2A receptor (5-HT2AR) activation may not be necessary for these beneficial effects.
This project focuses on the basic neuroscience implications and innovation aspects of this paradigm-shifting discovery. We will characterize the activity of known psychedelic-like compounds at TrkB and develop novel classes of potent TrkB-selective PAMs. The molecular basis underlying the TrkB binding and modulation mediated by the psychedelics and TrkBselective PAMs will be delineated. The neuronal and behavioral effects arising from their TrkB modulation will be studied and compared to those induced by 5-HT2AR agonists in ex vivo/in vivo studies, including by use of neuroimaging techniques.
In conclusion, the overall project aims are to explore the mode of action for the TrkB modulation through this novel allosteric site and the ex vivo/in vivo effects arising from this modulation, and to identify novel TrkB-selective PAMs and develop them further as novel drugs for mood disorders.