A One–Time Treatment Leads to a Full Set of Teeth in Dogs With Ectodermal Dysplasia!

December 2007
By Margret Casal, VMD, PhD, University of Pennsylvania

As many friends of the NFED know from Dr. Gaide’s and Dr. Schneider’s studies that were funded by the NFED, recombinant ectodysplasin A (Fc:EDA1) was injected pre– and postnatally to mice with the same form of ectodermal dysplasia (XHLED) as is found in humans and dogs. The protein was designed such that when injected IV into pregnant mouse mothers, the immunoglobulin portion would allow for transfer across the placenta into the affected fetus. Because there is virtually no intra uterine transfer of immunoglobulins in the dog, we chose to treat the XLHED dogs postnatally.

We also chose to use the dog model for further treatment trials using Fc:EDA1 because the disease is much more like that seen in human patients. The XLHED dogs have symmetrical hairlessness, nasal crusting, dry eye from decreased lacrimation, and cannot sweat. The tooth abnormalities are also quite similar, in that, the number of teeth is greatly reduced and those teeth that are present are generally all peg-shaped in affected dogs.

Tooth number and development in unaffected dogs and humans is very similar: deciduous (milk) teeth are formed before birth, erupt after birth and are followed by permanent (adult) teeth, whereas mice differ in that they only have 16 permanent teeth with incisors that grow continuously, and in that they have no canines and premolars. Also, the tooth abnormalities are minor in affected mice when compared to humans and dogs with XHLED.

In this current study that has been accepted for publication in the American Journal of Human Genetics, we were able to show that administering Fc:EDA1 to newborn XHLED puppies resulted in normalization of the permanent teeth in both number and shape. The effect of Fc:EDA1 was not just restricted to the adult teeth, but the medication also improved weight gain, restored tear flow preventing eye infections and dry eye, allowed for the formation of a small number of functional sweat glands (foot pads of dogs; normal site of sweat glands), and greatly improved respiratory health. However, the hairlessness was not corrected, most likely because hair development in the dog is a prenatal event. These exciting findings are important for the treatment of human patients because the diagnosis is often not made until after birth and treatment early in life may still result in improvement of clinical features of the disease.

The publication is titled "Significant correction of disease after postnatal administration of recombinant EDA in canine X-linked ectodermal dysplasia" and is written by M. L. Casal, J. R. Lewis, E. A. Mauldin, A. Tardivel, K. Ingold, M. Favre, F. Paradies, S. Demotz, O. Gaide, and P. Schneider.

Read More Articles