The science behind Dolinnov: finding FXYD2 in pain-sensing neurons
Publication
Contents
Dolinnov's approach to chronic pain rests on more than ten years of research at the Montpellier Institute of Neurosciences (INM, Inserm / University of Montpellier). This series looks at the three peer-reviewed papers that built the case for the company's target, FXYD2. The first one was published in PLoS One in 2012.
What the study found
Pain signals reach the spinal cord through sensory neurons grouped in the dorsal root ganglia (DRG), next to the spine. The team led by Patrick Carroll, with Stéphanie Ventéo as first author, looked for genes active in these neurons.
One of them was FXYD2. It encodes a small regulatory subunit of the sodium-potassium pump (Na,K-ATPase), the pump that keeps the electrical balance of every nerve cell. Until then, FXYD2 was known mainly in the kidney. The study showed, in mice, that it is also present in the DRG, but only in a few groups of sensory neurons, including pain-sensing neurons (nociceptors), and that its levels change after nerve injury.
Why it matters for Dolinnov
A good drug target should act where the problem is, and as little as possible elsewhere. This first paper showed that FXYD2 is found in a narrow set of sensory neurons, including neurons involved in pain. That restricted pattern is the starting point of Dolinnov's strategy: act on pain at its source, in the peripheral nervous system, without targeting the brain.
Reference
Ventéo S, Bourane S, Méchaly I, et al. Regulation of the Na,K-ATPase gamma-subunit FXYD2 by Runx1 and Ret signaling in normal and injured non-peptidergic nociceptive sensory neurons. PLoS One. 2012;7(1):e29852. doi:10.1371/journal.pone.0029852
Next in the series: how FXYD2 turned out to be required for neuropathic pain to persist (Scientific Reports, 2016).
About Dolinnov
Dolinnov is a preclinical-stage biotech company founded in October 2024 in Montpellier, France, by Grégoire Serra, Stéphanie Ventéo and Jean-Philippe Annereau. It develops Precision Pump Modulators, a new class of non-opioid treatments for chronic pain, starting with an antisense oligonucleotide targeting FXYD2 in pain-sensing neurons.
