“The aetiology and characteristics of testicular adrenal rest tumours”, Claashen (Nijmegen), montant attribué par IFCAH: 66 000 €

Patients with congenital adrenal hyperplasia often develop benign testicular tumors, called testicular adrenal rest tumors (TARTs), which cause infertility. Unfortunately, we only know little about these TARTs and as a result there is no suitable treatment. Therefore, in our study we will determine the characteristics of TART and how they develop. We will compare several tissue samples using a technique called RNA-sequencing. We hope to find a profile of characteristics specific for these TARTs that can help us to develop better diagnostic and therapeutic options.

“Prospective study of pregnancy outcomes in women treated early by dexamethasone for congenital adrenal hyperplasia”, Bachelot (Paris), montant attribué par IFCAH: 50 000 €

To avoid the virilization of the girl during fetal life in 21-OHdeficiency, prenatal treatment with dexamethasone (DEX) is proposed. In DEX-treated mothers, adverse effects of glucocorticoids have been reported with variable frequency and intensity. This study will be the first to evaluate propectively obstetrical, endocrinal and metabolical outcome in DEX-treated women. This leads to improve management of these women and prevention of the comorbidities.

“Sodium wasting, water balance and fludrocortisone needs in Congenital Adrenal Hyperplasia: the NaCAH Study”, Martinerie (Paris), montant attribué par IFCAH: 72 000 €

Congenital adrenal hyperplasia in its severe salt-wasting form is a challenge in order to maintain sodium balance. The pathophysiology of this impaired sodium balance is still poorly investigated as well as its therapeutic management, notably in the neonatal period. A clinical human study in classical CAH neonates, using LC-MS/MS technology will assess plasma and urinary steroid profiling (precursors and substitute hormones, notably Fludrocortisone dosages) during the first six months of life, before and under treatment; and in correlation with genotype. This project will lead to a better understanding of sodium handling and steroid secretion and excretion profiles in CAH neonates, in order to improve management of mineralocorticoid replacement.

“Optimizing fertility outcomes for women with CAH- an assessment of endometrial function and pregnancy complications “, G.Conway(Londres), montant attribué par IFCAH: 100 000 €

“Study of CAH adrenocortical cells reprogrammed from urine: a step towards cell therapy”, L .Guasti, (Londres) montant attribué à travers le partenariat avec l’AFM-Telethon: 100 000 €

Reprogramming describes the process where either a partially committed cell type or even a fully differentiated, specialized cell type is induced to transform into a different cell type that it would not otherwise become under normal physiological conditions. Direct reprogramming is usually achieved through forced expression of lineage-determining factors and is a way of obtaining cells of a given lineage. With the latter, we have been able to obtain cells with an adrenocortical phenotype starting from cells extracted from skin, blood and urine of healthy donors. With this proposal we aim at 1) characterising reprogrammed cells from patients with congenital adrenal hyperplasia and 2) using gene-editing techniques to cure the genetic defect.

“Adrenal Crisis Emergency spray”, Ross (Sheffield) (renouvellement du projet 2015), montant attribué par IFCAH en 2016: 60 000 €.

Adrenal Crisis Emergency Spray: ACEspray. Patients with congenital adrenal hyperplasia have a deficiency in the vital stress hormone cortisol and are at risk of an adrenal crisis. An adrenal crisis, cardiovascular collapse resulting in death if untreated, requires the administration of hydrocortisone injections. Patients are encouraged to carry an injection pack in case of a crisis but many patients find this difficult and are scared to administer the injection themselves. This project aims to develop a convenient to carry, easy to self-administer, nasal emergency spray to prevent adrenal crisis.