ParkinsonCanadaV1, Main, Merge, bibRecord, 001569

Human Mendelian pain disorders: a key to discovery and validation of novel analgesics

Identifieur interne : 001569 ( Main/Merge ); précédent : 001568; suivant : 001570

Human Mendelian pain disorders: a key to discovery and validation of novel analgesics

Auteurs : Y. P. Goldberg [Canada] ; S. N. Pimstone [Canada] ; R. Namdari [Canada] ; N. Price [Canada] ; C. Cohen [Canada] ; R. P. Sherrington [Canada] ; M. R. Hayden [Canada]

Source :

Clinical genetics [ 0009-9163 ] ; 2012.

RBID : Pascal:12-0366791

Descripteurs français

Pascal (Inist)
- Erythromélalgie, Homme, Douleur, Validation test, Analgésique, Congénital, Génétique.
Wicri :
- topic : Homme, Génétique.

English descriptors

KwdEn :
- Analgesic, Congenital, Erythromelalgia, Genetics, Human, Pain, Test validation.

Abstract

We have utilized a novel application of human genetics, illuminating the important role that rare genetic disorders can play in the development of novel drugs that may be of relevance for the treatment of both rare and common diseases. By studying a very rare Mendelian disorder of absent pain perception, congenital indifference to pain, we have defined Nav 1.7 (endocded by SCN9A) as a critical and novel target for analgesic development. Strong human validation has emerged with SCN9A gain-of-function mutations causing inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder, both Mendelian disorder of spontaneous or easily evoked pain. Furthermore, variations in the Navl.7 channel also modulate pain perception in healthy subjects as well as in painful conditions such as osteoarthritis and Parkinson disease. On the basis of this, we have developed a novel compound (XEN402) that exhibits potent, voltage-dependent block of Navl.7. In a small pilot study, we showed that XEN402 blocks Navl.7 mediated pain associated with IEM thereby demonstrating the use of rare genetic disorders with mutant target channels as a novel approach to rapid proof-of-concept. Our approach underscores the critical role that human genetics can play by illuminating novel and critical pathways pertinent for drug discovery.

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Pascal:12-0366791

Le document en format XML

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<front><div type="abstract" xml:lang="en">We have utilized a novel application of human genetics, illuminating the important role that rare genetic disorders can play in the development of novel drugs that may be of relevance for the treatment of both rare and common diseases. By studying a very rare Mendelian disorder of absent pain perception, congenital indifference to pain, we have defined Nav 1.7 (endocded by SCN9A) as a critical and novel target for analgesic development. Strong human validation has emerged with SCN9A gain-of-function mutations causing inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder, both Mendelian disorder of spontaneous or easily evoked pain. Furthermore, variations in the Navl.7 channel also modulate pain perception in healthy subjects as well as in painful conditions such as osteoarthritis and Parkinson disease. On the basis of this, we have developed a novel compound (XEN402) that exhibits potent, voltage-dependent block of Navl.7. In a small pilot study, we showed that XEN402 blocks Navl.7 mediated pain associated with IEM thereby demonstrating the use of rare genetic disorders with mutant target channels as a novel approach to rapid proof-of-concept. Our approach underscores the critical role that human genetics can play by illuminating novel and critical pathways pertinent for drug discovery.</div>
</front>
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Human Mendelian pain disorders: a key to discovery and validation of novel analgesics

Human Mendelian pain disorders: a key to discovery and validation of novel analgesics

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri