RT Journal Article
SR Electronic
T1 Prenatal Treatment of X-Linked Hypohidrotic Ectodermal Dysplasia Using Recombinant Ectodysplasin in a Canine Model
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 806
OP 813
DO 10.1124/jpet.118.256040
VO 370
IS 3
A1 Carol A. Margolis
A1 Pascal Schneider
A1 Kenneth Huttner
A1 Neil Kirby
A1 Timothy P. Houser
A1 Lee Wildman
A1 Gary L. Grove
A1 Holm Schneider
A1 Margret L. Casal
YR 2019
UL http://jpet.aspetjournals.org/content/370/3/806.abstract
AB 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.