Prenatal Treatment of X-Linked Hypohidrotic Ectodermal Dysplasia using Recombinant Ectodysplasin in a Canine Model.

Détails

ID Serval
serval:BIB_D7292BCE029F
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Titre
Prenatal Treatment of X-Linked Hypohidrotic Ectodermal Dysplasia using Recombinant Ectodysplasin in a Canine Model.
Périodique
The Journal of pharmacology and experimental therapeutics
Auteur(s)
Margolis C.A., Schneider P., Huttner K., Kirby N., Houser T.P., Wildman L., Grove G.L., Schneider H., Casal M.L.
ISSN
1521-0103 (Electronic)
ISSN-L
0022-3565
Statut éditorial
Publié
Date de publication
09/2019
Peer-reviewed
Oui
Volume
370
Numéro
3
Pages
806-813
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by defects in the EDA gene that inactivate the function of ectodysplasin A1 (EDA1). This leads to abnormal development of eccrine glands, hair follicles, and teeth, and to frequent respiratory infections. Previous studies in the naturally occurring dog model demonstrated partial prevention of the XLHED phenotype by postnatal administration of recombinant EDA1. The results suggested that a single or two temporally spaced injections of EDI200 prenatally might improve the clinical outcome in the dog model. Fetuses received ultrasound-guided EDI200 intra-amniotically at gestational days 32 and 45, or 45 or 55 alone (of a 65-day pregnancy). Growth rates, lacrimation, hair growth, meibomian glands, sweating, dentition, and mucociliary clearance were compared in treated and untreated XLHED-affected dogs, and in heterozygous and wild-type control dogs. Improved phenotypic outcomes were noted in the earlier and more frequently treated animals. All animals treated prenatally showed positive responses compared with untreated dogs with XLHED, most notably in the transfer of moisture through paw pads, suggesting improved onset of sweating ability and restored meibomian gland development. These results exemplify the feasibility of ultrasound-guided intra-amniotic injections for the treatment of developmental disorders, with improved formation of specific EDA1-dependent structures in dogs with XLHED.
Mots-clé
animal models, drug tolerance/dependence, recombinant proteins
Pubmed
Web of science
Open Access
Oui
Création de la notice
05/05/2019 14:28
Dernière modification de la notice
10/10/2019 5:10
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