title: Significant correction of disease after postnatal administration of recombinant ectodysplasin A in canine X-linked ectodermal dysplasia.
abstract: Patients with defective ectodysplasin A (EDA) are affected by X-linked hypohidrotic ectodermal dysplasia (XLHED), a condition characterized by sparse hair, inability to sweat, decreased lacrimation, frequent pulmonary infections, and missing and malformed teeth. The canine model of XLHED was used to study the developmental impact of EDA on secondary dentition, since dogs have an entirely brachyodont, diphyodont dentition similar to that in humans, as opposed to mice, which have only permanent teeth (monophyodont dentition), some of which are very different (aradicular hypsodont) than brachyodont human teeth. Also, clinical signs in humans and dogs with XLHED are virtually identical, whereas several are missing in the murine equivalent. In our model, the genetically missing EDA was compensated for by postnatal intravenous administration of soluble recombinant EDA. Untreated XLHED dogs have an incomplete set of conically shaped teeth similar to those seen in human patients with XLHED. After treatment with EDA, significant normalization of adult teeth was achieved in four of five XLHED dogs. Moreover, treatment restored normal lacrimation and resistance to eye and airway infections and improved sweating ability. These results not only provide proof of concept for a potential treatment of this orphan disease but also demonstrate an essential role of EDA in the development of secondary dentition.
authors.affiliation: School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. casalml@vet.upenn.edu
authors.forename: Margret L
authors.initials: ML
authors.lastname: Casal
authors.forename: John R
authors.initials: JR
authors.lastname: Lewis
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mauldin
authors.forename: Aubry
authors.initials: A
authors.lastname: Tardivel
authors.forename: Karine
authors.initials: K
authors.lastname: Ingold
authors.forename: Manuel
authors.initials: M
authors.lastname: Favre
authors.forename: Fabrice
authors.initials: F
authors.lastname: Paradies
authors.forename: Stephane
authors.initials: S
authors.lastname: Demotz
authors.forename: Olivier
authors.initials: O
authors.lastname: Gaide
authors.forename: Pascal
authors.initials: P
authors.lastname: Schneider
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003817:Dentition; D004195:Disease Models, Animal; D004285:Dogs; D004476:Ectodermal Dysplasia / Q000628:therapy*; D053331:Ectodysplasins / Q000008:administration & dosage* / Q000494:pharmacology*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000628:therapy*; D006801:Humans; D007275:Injections, Intravenous; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008334:Mandible / Q000000981:diagnostic imaging / Q000187:drug effects; D051379:Mice; D009079:Mucociliary Clearance / Q000187:drug effects; D011859:Radiography; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000494:pharmacology*; D013546:Sweating / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D053331:Ectodysplasins; D011994:Recombinant Proteins