Project: PHArmacological Augmentation of Stress Resilience - Proof of Principle

Acronym	PHASR-PP
Project Topic	The project builds on findings from animal research suggesting that a) pharmacological inhibition of the mTOR pathway and b) protection of the integrity of the Blood-Brain Barrier (BBB) in individuals exposed to an environmental challenge promotes their stress resilience. mTOR inhibition may act by protecting BBB integrity. Translating these results to the human, the project aims to test in a randomized placebo-controlled double-blind multi-center multimodal pre-registered proof-of-principle clinical trial whether administration of a commercially available indirect mTOR inhibitor protects vulnerable young adults against stress-related mental health problems and whether this hypothesized effect is mediated by reduced BBB leakiness, as assessed using neuroimaging. Psycho-social individual differences will also be considered, as potential treatment-effect moderators. The project has the potential to establish a novel method for the prevention of stress-related mental dysfunctions, via repurposing of a well-known and inexpensive off-patent drug with a highly favorable safety profile, and thereby to make an important contribution to the improvement of public health. Involving trial participants and European patient family organizations, potential ethical and social implications of the pharmacological prevention approach will be investigated, with a special emphasis on gender factors, and steps towards an ethical guideline for pharmacological resilience interventions will be taken.
Network	NEURON Cofund2
Call	Neuron Cofund2 Joint Call 2023

Project partner

Number	Name	Role	Country
1	Leibniz-Institut für Resilienzforschung gGmbH	Coordinator	Germany
2	UNIVERSITÄTSMEDIZIN DER JOHANNES GUTENBERG-UNIVERSITÄT MAINZ (UMC-Mainz)	Partner	Germany
3	UNIVERSITÄT ZÜRICH (UZH)	Partner	Switzerland
4	UNIWERSYTET WARSZAWSKI (UNIWARSAW)	Partner	Poland
5	LATVIJAS UNIVERSITATE (LU)	Partner	Latvia