(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.)

Dr. Margret Casal

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.

Bruce Wayne has contributed years of service in helping children with XLHED. He is now retired and enjoys walks in the forest with Chloe (pictured above with Bruce) and Conner that were retired from the program earlier and his human mom, Alice.

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.

Chloe and Bruce Wayne with their haired friend, Virgil.

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

5 comments on “News from the XLHED Dog World”

  1. 1
    Richard Henkel on March 21, 2018

    What were the times of treatment with EDI200, and what are the implications for human trials?

    1. 2
      Jodi Edgar Reinhardt on March 22, 2018

      Hi, Richard. We are asking Dr. Casal your question and will post the answer when I have it. Thanks!

  2. 3
    Pamela Spilbeler on March 21, 2018

    Congratulations on these very impressive results. Keep up the good work and know that XLHED humans appreciate your efforts

  3. 4
    James Finch on March 21, 2018

    Has a paper been published yet and do you have a link?

    Is interesting I’m seeing biohacking now at DEF CON as well as Gene Therapy on HackaDay that is open source.

    Seem’s the EDI200 is consistent to vector in earlier on as I recall for hair development at least… the earlier the better (unless regional selection potential for head, and no body, hair).

    I’m going to have to read into EDA extraction, purification and dosing techniques as well as requirements for an open source method. Same goes for an incubator as seems more of a troublesome trajectory.

    Neat to read about new results. Awesome to read with different dog breeds, looking forward to reviewing more data.

    1. 5
      Jodi Edgar Reinhardt on March 22, 2018

      From what we understand, the journal article is forthcoming. We will post a link to it once we have it. Thanks!

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