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Thérapie génique de la douleur

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Résumé

La thérapie génique pour combattre la douleur peut paraître surprenante et inadaptée alors que nous disposons des opiacés et d’autres molécules actives. Cependant, la possibilité de délivrer dans une structure bien ciblée une protéine-médicament qui agira en permanence (et si possible à la demande) au contact direct des cellules visées, ou même en leur sein, permet d’éviter les inconvénients inhérents à certaines drogues, et, surtout, d’améliorer certaines approches thérapeutiques voire d’en ouvrir de nouvelles. Les améliorations récentes et constantes des vecteurs permettent d’espérer le développement de systèmes de transfert de gènes plus performants, et surtout plus sûrs pour leur utilisation chez l’homme. Les premiers résultats expérimentaux obtenus avec les gènes des précurseurs des opioïdes témoignent de l’efficacité de ces techniques pour surexprimer ces peptides dans les neurones sensoriels ou au niveau médullaire. Les peptides opioïdes, produits dans ces tissus, ont des effets antihyperalgésiques dans divers modèles de douleurs chroniques. Cependant, bien d’autres molécules impliquées dans le traitement de l’information douloureuse, ont été, ou viennent d’être, identifiées et les approches que nous décrivons paraissent particulièrement adaptées pour vérifier l’intérêt thérapeutique potentiel de la modification de leur expression.

Summary

Gene therapy to alleviate pain could appear surprising and perhaps not appropriate when opioids and other active molecules are available. However, the possibility of introducing a therapeutic protein into some targeted structures, where it would be continuously synthesised and exert its biological effect in the near vicinity of, or inside the cells, might avoid some drawbacks of «classical» drugs. Moreover, the gene-transfer techniques might improve present therapies or lead to novel ones. The recent significant and constant advances in vector systems design suggest that these techniques will be available in the near future for safe application in humans. The first experimental protocols attempting the transfer of opioid precursors genes, leading to their overexpression at the spinal level, demonstrated the feasibility and the potential interest of these approaches. Indeed, overproduction of opioid peptides in primary sensory neurones or spinal cord induced antihyperalgesic effects in various animal models of persistent pain. However, numerous other molecules involved in pain processing or associated with chronic pain have been identified and the gene-based techniques might be particularly adapted for the evaluation of the possible therapeutic interest of these new potential targets.

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Correspondence to M. Pohl.

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Pohl, M., Braz, J. Thérapie génique de la douleur. Doul. et analg. 14, 213–218 (2001). https://doi.org/10.1007/BF03012693

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Mots-clés

  • Thérapie génique
  • transfert de gènes
  • peptides opioïdes
  • antihyperalgésie
  • rats polyarthritiques

Key-words

  • Gene therapy
  • pain chronic
  • herpes simplex virusderived vector
  • opioid peptides