Project A04

Novel diagnostic, therapeutic and monitoring options in Congenital Adrenal Hyperplasia

Project A04 focuses on congenital adrenal hyperplasia (CAH). This is a genetically determined, autosomal recessive disorder in which various mutations in the enzymes involved in steroid hormone biosynthesis in the adrenal cortex lead to disruptions in the hormone metabolism of affected individuals. The most common cause is a deficiency of the enzyme 21-hydroxylase. Current treatment options are not optimal, as the hormone replacement therapies used do not closely resemble natural hormone secretion, and undesirable side effects from glucocorticoid therapy are very common.

Central aim of project A04 is to use the established mouse models for congenital adrenal hyperplasia (CAH) as well as the clinical data and biosamples collected in the CAH registry to gain a better understanding of the pathophysiological processes and to develop new therapeutic options for CAH. We will use our mouse models to establish a cell therapy with human induced steroid-producing cells derived from human embryonic stem cells. We will study fertility disorders and dysregulated immune phenotype in CAH mice. With the CAH-registry, we will perform important translational studies also focusing on fertility, immune phenotype and biomarkers in CAH. The final goal is to enable personalised treatment options for CAH patients and thus to improve their quality of life.

Aims

(I) Establish cell therapy in our CAH mouse models

(II) Investigate fertility in homozygous CAH mice and impact of glucocorticoid treatment

(III) Determine the influence of hormonal control on the immune phenotype and metabolism in CAH

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