The science behind Dolinnov: an antisense approach for long-lasting pain relief

The first two papers showed that FXYD2 sits in pain-sensing neurons and is needed for neuropathic pain to persist. The third step was to turn this target into a treatment. The study, published in JCI Insight in 2023 by the Montpellier Institute of Neurosciences with the ARNA laboratory in Bordeaux (Inserm / University of Bordeaux), is the work on which Dolinnov was founded.

The approach: antisense oligonucleotides

An antisense oligonucleotide (ASO) is a short, synthetic strand of genetic material designed to bind the messenger RNA of one gene and reduce the amount of protein the cell makes from it. The team designed an ASO against a part of the FXYD2 messenger RNA that is identical in rats and humans. To help it reach the sensory neurons of the dorsal root ganglia, they attached a lipid to it (a « lipid-ASO »).

What the study found

• In rat models of both neuropathic pain (nerve injury) and inflammatory pain, the lipid-ASO led to a virtually complete alleviation of pain symptoms.
• It worked when injected into the fluid around the spinal cord (intrathecal) and when injected into the bloodstream (intravenous).
• No obvious side effects were observed.
• With an additional chemical modification (a « gapmer » design), the effect of a single injection lasted up to 10 days.

Why it matters for Dolinnov

This paper provides the preclinical proof of concept for Dolinnov's approach: lowering FXYD2 in pain-sensing neurons relieves chronic pain of different origins, and the effect lasts. Dolinnov was created in 2024 to develop this approach into a medicine. Its lead candidate builds on the lipid-ASO described here.

Reference

Derre A, Soler N, Billoux V, et al. FXYD2 antisense oligonucleotide provides an efficient approach for long-lasting relief of chronic peripheral pain. JCI Insight. 2023;8(9):e161246. doi:10.1172/jci.insight.161246

Previous: FXYD2 is needed 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.

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