Medics in Germany have cured three unborn children with X-Linked Hypohidrotic ectodermal dysplasia (XLHED), a genetic condition that causes children to be born with fang-like front teeth, sparse hair, and missing sweat glands. This is not only the first time an unborn child has been treated for XLHED in utero but the very first time an inherited disorder has been reversed in the womb.
The procedure was performed at a German clinic at the University of Erlangen-Nürnberg in 2016, but it has only recently been published in a case report in the New England Journal of Medicine. Two years on and they can declare the experiment a success.
XLHED is the most common type of HED, an incredibly rare genetic condition usually passed from generation to generation on recessive genes. Children with two abnormal genes are born with an extreme heat intolerance that can, in certain circumstances, trigger life-threatening hyperthermia. The heat intolerance is caused by a mutation in the gene, which affects the body's ability to produce a specific protein essential to making sweat glands.
“It can be life-threatening when they are young. They got hot very fast if you leave them in a car,” Holm Schneider, a family physician and lead author of the paper, explained, reports the MIT Technology Review.
“But when they are bigger, they instinctively know to cool off.” For example, by soaking themselves in water or resting against a cold surface.
Corinna T is a nurse from Germany. Her son was diagnosed with the condition aged two. “He was crying incessantly because he had become too hot,” she said.
Later, she became pregnant again. This time with twins. At 21 weeks, she had an ultrasound scan confirming both had the same inherited disorder as their brother.
It was then she had an idea.
An earlier clinical trial had attempted to treat young children with XLHED using a protein replacement drug – but failed. The therapy didn’t cure the children so the study was dumped and the drug-maker (Edimer) closed for business. Corinna remembered another experiment that had successfully injected the drug into pregnant mice and wondered if the same could be done in humans.
There was hesitation but the university agreed to perform the treatment under a “compassionate use” exemption, using some drugs leftover from the original trial.
Medics exploited the fact the missing protein is only needed at the point in pregnancy when the fetuses' sweat glands are being developed (weeks 20 to 30), injecting it directly into the amniotic sac.
When the twins and a third baby (who had also received treatment) were born, they were able to sweat normally. Two years on and the toddlers are able to tolerate heat as normal, sweat glands intact.
“Here you have an incurable disorder, no drug available, and here is something working—three out of three,” said Schneider.
It's a huge leap forward for in utero medication and while many groups may be hesitant because of the risks posed to the mother, it could pave the way for fetal gene therapy in the future.
[H/T: MIT Technology Review]
