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

Details

Serval ID
serval:BIB_D7292BCE029F
Type
Article: article from journal or magazin.
Collection
Publications
Title
Prenatal Treatment of X-Linked Hypohidrotic Ectodermal Dysplasia using Recombinant Ectodysplasin in a Canine Model.
Journal
The Journal of pharmacology and experimental therapeutics
Author(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
Publication state
Published
Issued date
09/2019
Peer-reviewed
Oui
Volume
370
Number
3
Pages
806-813
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
Animals, Dogs, Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive/drug therapy, Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive/genetics, Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive/pathology, Ectodysplasins/administration & dosage, Ectodysplasins/therapeutic use, Female, Fetus/diagnostic imaging, Foot, Gestational Age, Pregnancy, Recombinant Proteins/administration & dosage, Recombinant Proteins/therapeutic use, Sweating, Treatment Outcome, Ultrasonography, Interventional
Pubmed
Web of science
Open Access
Yes
Create date
05/05/2019 15:28
Last modification date
18/01/2020 7:17
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