Restoring endocannabinoid homeostasis to create the first effective & safe pharmacotherapy for PTSD

Purpose and goal:

The aim of Pronexus´ part of the project was to search for neurochemical correlates (endocannabinoids and related substances) to behavioral studies and fMRI data in brain structures relevant to PTSD, namely the prefrontal cortex, hippocampus and amygdala, as well as, to analyze the test substance SYT-510 and its effects in brain samples and samples from cerebrospinal fluid (CSF) and plasma.

Expected results and effects:

Liquid chromatography-mass spectrometry (UHPLC-MS/MS) methods were developed for the analysis of test substances SYT-510, SYT-520 and the endocannabinoids AEA, 2-AG, 1-AG and related substances AA, LEA, OEA, PEA, PGE2, PGD2, as well as corticosterone and progesterone. The second UHPLC-MS/MS method was developed for the analysis of the neurotransmitters dopamine, norepinephrine, 5-HT, histamine, glutamate and GABA in brain tissue samples.

These methods enable quantitative evaluation of potential effects of SYT-510 on the selected biomarkers of endocannabinoid signaling. Approach and implementation:

The implementation of the project was carried out in close collaboration with partners Porsolt and UMC Amsterdam and coordinated by Synendos. Porsolt provided biological samples from behavioral studies of various PTSD models, UMC contributed with samples from fMRI studies of the PTSD model (restrained stress) and treatment with SYT-510. Pronexus analyzed endocannabinoids and related biomarkers as well as SYT-510 in brain tissue samples and plasma, analyzes of CSF samples from UMC will be completed within the next two months.