Our scientific team* presented during Neuroscience 2022 the abstract “Pharmacology of TTX-resistant and TTX-sensitive sodium currents in non-human primate dorsal root ganglion sensory neurons”
* Dong Liu, MD, Chen Tian, PhD, Adina Hazan, PhD, Mahsa Sadeghi, PhD, Christian Petroski, Robert Petroski, PhD, Neuroservices-Alliance (Neuroservice USA – in vitro cell electrophysiology)
Chronic pain is poorly managed by current therapies. The opiate epidemic has highlighted the need for alternative therapies for treating pain. Genetic and functional studies have established an important role of voltage-gated sodium channels in human pain disorders.
Tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium channels expressed in dorsal root ganglion (DRG) sensory neurons are currently being pursued as promising therapeutic targets for treating human pain. Many drug discovery programs rely on pharmacology data from rodent neurons for generating the structure-activity relationships (SAR) during lead optimization.
However, the pharmacological activity of compounds on rodent target proteins sometimes differs from their human orthologs and poses a challenge for identifying the best pre-clinical candidates to advance to human clinical trials.
Here we describe the development and validation of an electrophysiological assay of TTX-R sodium channels from non-human primate (NHP) and dog DRG sensory neurons and show the efficacy and potency of 14 compounds for blocking TTX-R sodium currents. These results reveal differences in compound activity on native sodium channels from different species.