News from the XLHED Dog World

March 20, 2018March 20, 2018 Category: Research Posted by NFED

(Editor’s Note: The National Foundation for Ectodermal Dysplasias has supported Dr. Margret Casal and her team for more than 16 years. Their important discoveries in the dog model of x-linked hypohidrotic ectodermal dysplasia laid the groundwork for studying the use of EDI200 in humans in the Newborn XLHED Clinical Trial.)

By Carol A Margolis¹, Kenneth Huttner², Neil Kirby², Pascal Schneider³, Timothy P Houser⁴, Lee Wildman⁴, Gary L. Grove⁴, Elizabeth A. Mauldin¹, Holm Schneider⁵, Margret L. Casal¹

In our previous studies, we showed that administration of recombinant ectodysplasin (Fc:EDA1; EDI200)  in x-linked hypohidrotic ectodermal dysplasia (XLHED) dogs during the first two weeks of life resulted in almost complete correction of dentition, the development of tracheal, bronchial and esophageal glands, correction of dry eye, and increased ability to sweat. However, there was no effect on hair restoration. The results suggested that perhaps earlier administration of EDI200 might have more of an impact on correction of XLHED.

Treating In Utero

In the current study, we injected EDI200 into the amniotic sacs of affected dog fetuses under ultrasound guidance to assess safety and efficacy. We chose different time points that correspond to important developmental milestones for hair, tooth, and sweat gland development.  We compared growth rates, general health, Meibomian glands, sweating, and dentition in treated and untreated XLHED and normal dogs.

We also examined mucociliary clearance, which is an indirect, non-invasive method to assess the presence of tracheal and bronchial glands. Finally, we used a novel method, Dynamic Capacitance Imaging (DCI), to examine sweating from the footpads. DCI is a non-invasive technique, which allows one to image surface texture and moisture over time, providing clear visualization of sweat gland distribution and activity in humans.

What We Learned

We found that those fetuses treated earlier during pregnancy and those treated at two different time points showed more improvement than those receiving treatment later in pregnancy. However, all treated groups of XLHED dogs showed normal transfer of moisture through paw pad, suggesting normal sweating ability, and all had normal Meibomian gland development. The results show that ultrasound-guided intra-amniotic injections are safe and partially effective.

The results also demonstrated that DCI was able to differentiate between paw-pad moisture output rates (suggestive of sweating) of treated, untreated and unaffected dogs.  More experiments will need to be performed to pinpoint the exact time point of treatment during fetal life to achieve the greatest improvement.

 

¹School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; ²Edimer Pharmaceuticals, Cambridge, MA, USA; ³Department of Biochemistry, University of Lausanne, Switzerland; ⁴cyberDERM, Inc., Broomall, PA, USA; ⁵Universitätsklinikum Erlangen, Kinder-und Jugendklinik, Erlangen, Germany