Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia

N Engl J Med. 2018 Apr 26;378(17):1604-1610. doi: 10.1056/NEJMoa1714322.

Abstract

Genetic deficiency of ectodysplasin A (EDA) causes X-linked hypohidrotic ectodermal dysplasia (XLHED), in which the development of sweat glands is irreversibly impaired, an condition that can lead to life-threatening hyperthermia. We observed normal development of mouse fetuses with Eda mutations after they had been exposed in utero to a recombinant protein that includes the receptor-binding domain of EDA. We administered this protein intraamniotically to two affected human twins at gestational weeks 26 and 31 and to a single affected human fetus at gestational week 26; the infants, born in week 33 (twins) and week 39 (singleton), were able to sweat normally, and XLHED-related illness had not developed by 14 to 22 months of age. (Funded by Edimer Pharmaceuticals and others.).

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amniotic Fluid
  • Antigens, CD / therapeutic use*
  • Ectodermal Dysplasia 1, Anhidrotic / diagnostic imaging
  • Ectodermal Dysplasia 1, Anhidrotic / genetics
  • Ectodermal Dysplasia 1, Anhidrotic / therapy*
  • Ectodysplasins / deficiency
  • Ectodysplasins / genetics*
  • Ectodysplasins / therapeutic use*
  • Female
  • Fetal Therapies / methods*
  • Genetic Therapy / methods*
  • Humans
  • Immunoglobulin Fc Fragments / therapeutic use*
  • Injections
  • Male
  • Mutation
  • Pregnancy
  • Prenatal Diagnosis*
  • Radiography
  • Receptors, Fc / therapeutic use*
  • Recombinant Fusion Proteins / therapeutic use*
  • Recombinant Proteins / therapeutic use
  • Sweat Glands / abnormalities
  • Sweat Glands / diagnostic imaging
  • Tooth Germ / diagnostic imaging

Substances

  • Antigens, CD
  • Ectodysplasins
  • Fc(alpha) receptor
  • Fc-EDA
  • Immunoglobulin Fc Fragments
  • Receptors, Fc
  • Recombinant Fusion Proteins
  • Recombinant Proteins