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Rare genetic disorder treated before birth for first time

30 April 2018
Appeared in BioNews 947

Three children have been cured of the worst symptoms of a developmental genetic condition with a 'remarkable' treatment while still in the womb.

Two women – one pregnant with a single child and one with twins – received injections of a protein that their fetuses were unable to produce themselves, due to a condition known as XLHED (X-linked hypohidrotic ectodermal dysplasia). The protein was administered straight into the amniotic fluid around the fetus, according to a study published in the New England Journal of Medicine. 

The condition is caused by a mutation in a gene involved in developing skin, hair, teeth and nails, carried on the X chromosome. One of the most serious symptoms is having no or very few sweat glands, making it difficult to regulate temperature. XLHED can be fatal if the children become too hot, especially when they are too young to seek out other ways to cool off. 

Sweat glands develop in a short window between 20 and 30 weeks of pregnancy. Experiments in mice had previously shown that injecting the protein during this phase of development in utero led to offspring that had the glands and could sweat normally. 

When the same was done for the two women, the children were also born with working glands. The twins' treatment was particularly successful. As the children grew, their ability to sweat became more and more obvious. At one point, their parents noted that they had completely soaked a car seat with sweat on a hot day. 

'A full rescue of sweating ability – that was so great, just unbelievable,' Corinna, mother of the twins, told STAT.

'We were hesitant,' Professor Holm Schneider, who carried out the study at the University Hospital Erlangen in Germany, told MIT Review. 'In [Corinna's] situation you think twice. You think more about the risks involved – three lives – but also the chances that it may bring.'

The third child also developed sweat glands, albeit fewer of them. The child's mother only received one dose of the protein while pregnant due to limited availability, whereas Corinna – the first to be treated – received three. After an unsuccessful trial of the protein with newborn babies with XLHED, the drug's maker had closed down and considered it a failure. As a result, only very small amounts of the drug remained left over from the trial. 

Professor Schneider and his colleagues now hope to develop the drug with a medical charity. As XLHED only affects about 1 in 17,000 people, commercial manufacture of the drug is unlikely ever to be profitable. A few doses of the drug during the crucial developmental window before birth are expected to have life-long effects, although the researchers acknowledge that they will have to wait many decades to confirm this. 

'That's the remarkable part here, that a genetic disease can be at least partially corrected by a short-term protein treatment,' said development biologist Dr Marja Mikkola at the University of Helsinki in Finland, who wrote an editorial on the study in the same issue of the journal. 'This study paves the way for a larger trial of this novel approach.'

The study also opens the door to investigating whether other genetic developmental conditions could be treated in a similar way. 

'There are a number of conditions for which we would seek treatment in utero, but traditionally these have been non-genetic, non-inherited conditions,' Dr Maisa Feghali at the University of Pittsburgh in Pennsylvania, who was not involved in the study, told STAT.

'It's quite a remarkable advance.'

SOURCES & REFERENCES
‘A full rescue’: Drug injected before birth treats rare genetic disorder
STAT News |  25 April 2018
In a medical first, drugs have reversed an inherited disorder in the womb
MIT Review |  25 April 2018
Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia
New England Journal of Medicine |  26 April 2018
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