Prenatal therapy in developmental disorders: drug targeting via intra-amniotic injection to treat X-linked hypohidrotic ectodermal dysplasia

Excerpt

Disorders that irremediably affect fetuses make early stage therapies desirable. X-linked hypohidrotic ectodermal dysplasia (XLHED), the most common inherited disorder of ectoderm development affecting the skin and its appendages, glands, and teeth, is caused by a lack of the signaling molecule ectodysplasin A1 (EDA1). In the Tabby XLHED mouse model, repeated intravenous administration of EDA1 to pregnant mice has been shown to correct the developmental abnormalities in the offspring. Maternal drug administration, however, exposes mothers to potential drug toxicity and is limited by the variability in transplacental drug delivery. Alternative approaches to fetal treatment should entail low risk drug delivery with reproducible pharmacokinetics. We hypothesized that a single injection of an EDA1 replacement molecule into the amniotic fluid could allow sustained drug exposure at levels sufficient for correction of XLHED. …