Neuropathic pain is a chronic illness affecting 7-10% of the population in France and for which there is no effective treatment. Researchers at the Institute for Neurosciences of Montpellier (Inserm/University of Montpellier) and the Laboratory for Therapeutic Innovation (CNRS/University of Strasbourg) have uncovered the mechanism behind the onset and continuation of pain. Thanks to their discovery, they have developed an innovative treatment prototype which produces, in animal models, an immediate and long-lasting effect on pain symptoms. This study was published on March 12, 2018 in Nature Communications.
French researchers have recently revealed the unexpected role played by the molecule FLT3 in chronic pain – a molecule known for its role in various blood functions and produced by the hematopoietic stem cells which generate all blood cells. Neuropathic pain is caused by peripheral nerve lesions caused by diseases such as diabetes, cancer, or shingles, or to accident-related trauma or surgery. In this study, the researchers showed that immune cells in the blood which flood the nerve at the lesion site synthesize and release another molecule, FL, which binds with and activates FLT3, triggering a chain reaction in the sensory system, causing pain. They revealed that FLT3 induces and maintains pain by acting far upstream on other components in the sensory system which are known for making pain chronic (a phenomenon known as “chronicization”).
After discovering the role of FLT3, researchers created an anti-FLT3 molecule (BDT001) to target the FL binding site, using detailed computer analysis of three million possible configurations. This molecule blocks the connection between FL and FLT3, thereby preventing the chain of events which leads to chronic pain. When administered to animal models, BDT001, after three hours, reduced typical neuropathic pain symptoms such as hyperalgesia, a heightened sensibility to pain, as well as allodynia, pain caused by stimuli which normally do not provoke pain, with effects lasting 48 hours after a single dose.
Neuropathic pain, which affects approximately 4 million people in France, is a debilitating disease with significant social costs. Current forms of treatment, essentially based on off-label uses of medication such as anti-depressants and anti-epileptics, are ineffective: less than 50% of patients obtain a significant reduction in their pain. Furthermore, such treatments can cause substantial side effects. The innovative therapy based on this research is being developed by Biodol Therapeutics, a start-up firm which may, as a result, finalize the very first specific therapy against neuropathic pain, and, in the long term, provide relief to many people.
 Researchers from the Institute of Functional Genomics (CNRS/Inserm/University of Montpellier) also took part in the research.
 This project was financed by the French National Research Agency (ANR) and the SATT AxLR in Montpellier. INSERM licensed the patent rights resulting from this discovery (WO2011/083124 and WO 2016/016370) to Biodol Therapeutics, a new start-up operating in Montpellier and Strasbourg and supported by BPI and the Region of Occitanie.
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Inhibition of neuronal FLT3 receptor tyrosine kinase alleviates peripheral neuropathic pain in mice.
Cyril Rivat, Chamroeun Sar Ilana Mechaly, Jean-Philippe Leyris, Lucie Diouloufet, Corinne Sonrier, Yann Philipson, Olivier Lucas, Sylvie Mallié, Antoine Jouvenel, Adrien Tassou, Henri Haton, Stéphanie Venteo, Jean-Philippe Pin, Eric Trinquet, Fabienne Charrier-Savournin, Alexandre Mezghrani, Willy Joly, Julie Mion, Martine Schmitt, Alexandre Pattyn, Frédéric Marmigère, Pierre Sokoloff, Patrick Carroll, Didier Rognan & Jean Valmier.
Nature communications, le 12 mars 2018.