Körber Iris, Klein Ophir D, Morhart Patrick, Faschingbauer Florian, Grange Dorothy K, Clarke Angus, Bodemer Christine, Maitz Silvia, Huttner Kenneth, Kirby Neil, Durand Caroline, Schneider Holm
Center for Ectodermal Dysplasias, University Hospital Erlangen, Germany.
University of California, San Francisco, CA, USA.
Br J Clin Pharmacol. 2020 Oct;86(10):2063-2069. doi: 10.1111/bcp.14301. Epub 2020 Apr 24.
In X-linked hypohidrotic ectodermal dysplasia, the most frequent ectodermal dysplasia, an inherited deficiency of the signalling protein ectodysplasin A1 (EDA1) impairs the development of the skin and its appendages, various eccrine glands, and dentition. The severe hypohidrosis common to X-linked hypohidrotic ectodermal dysplasia patients may lead to life-threatening hyperthermia, especially during hot weather or febrile illness. Fc-EDA, an EDA1 replacement protein known to prevent the disease in newborn animals, was tested in 2 clinical trials (human adults and neonates) and additionally administered under compassionate use to 3 infants in utero. The data support the safety of Fc-EDA and efficacy if applied prenatally. Anti-drug antibodies were detected after intravenous administration in adult males and nonpregnant females, but not in pregnant women when Fc-EDA was delivered intra-amniotically. Most importantly, there was no detectable immune response to the investigational drug in neonates treated by intravenous infusions and in infants who had received Fc-EDA in utero. In conclusion, the safety profile of this drug encourages further development of prenatal EDA1 replacement therapy.
在最常见的外胚层发育异常——X连锁低汗型外胚层发育不良中，信号蛋白外胚层发育不良蛋白A1（EDA1）的遗传性缺陷会损害皮肤及其附属器、各种汗腺和牙列的发育。X连锁低汗型外胚层发育不良患者常见的严重少汗可能导致危及生命的体温过高，尤其是在炎热天气或发热性疾病期间。Fc-EDA是一种已知可在新生动物中预防该病的EDA1替代蛋白，已在2项临床试验（成人和新生儿）中进行了测试，并根据同情用药原则对子宫内胎儿中的3名婴儿进行了额外给药。数据支持Fc-EDA的安全性以及产前应用的有效性。在成年男性和未怀孕女性静脉给药后检测到抗药抗体，但当Fc-EDA通过羊膜内给药时，在孕妇中未检测到。最重要的是，在接受静脉输注治疗的新生儿和在子宫内接受Fc-EDA的婴儿中，未检测到对该研究药物的免疫反应。总之，这种药物的安全性概况鼓励进一步开展产前EDA1替代疗法的研发。
