Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells

Primary or secondary adrenal insufficiency (AI) results from adrenal failure or impairment of the hypothalamic-pituitary axis, respectively. The most frequent cause of primary AI is autosomal recessive congenital adrenal hyperplasia (CAH). Patients with AI need life-long treatment with exogenous steroids, which can be challenging, given that currently available formulations do not mimic physiologic cortisol secretion. The ability to generate donor-specific and functional adrenocortical-like cells would facilitate: (1) the next generation of cell-based treatments for AI; (2) the modeling of adrenal-specific diseases; and (3) the testing of personalized interventions on cells derived from patients. Donor- and disease-specific steroidogenic cells as surrogates for disease modeling have been lacking up to now. More significantly, their use could be exploited for the development of cell- based treatment modalities for AI.