Following its call for projects, IFCAH received 16 letters of intent. Among them, 6 were pre-selected by the Scientific Committee. Final selection was based on a double evaluation by 2 international experts and audition of the candidates by the Scientific Committee.
Project 1: Blocking the ACTH receptor for blocking androgen production
In spite of the mineralocorticoid and glucocorticoid replacement therapy, a negative feedback stimulating ACTH production, induces an excessive adrenal androgen synthesis, compromising growth and fertility in patients with CAH. This project aims to search for novel drugs for cutting off this abnormal adrenal androgen production, by blocking the ACTH receptor. Such antagonists ACTH molecules will be tested in established cell systems. The results should allow prediction of their future use in patients.
Investigator: Pr C Flück, Bern University, Switzerland
Funding: 130,000 €
Project 2: A new emergency treatment for adrenal crisis
Adrenal crisis is a life-threatening condition that affects patients with CAH. Current treatment is by immediate intravenous or intramuscular injection of hydrocortisone. However, patients are scared of using injections despite education and the intervention is inconvenient to carry. The researchers propose to develop a convenient, portable and easy to use treatment. This project will evaluate the feasibility of producing a stable and well-tolerated product that could be easier to use in emergency situations.
Investigator Pr R Ross, Sheffield University, UK
Funding: 60.000 euros
Project 3: Corticosterone, a better treatment for CAH ?
It is widely acknowledged that current glucocorticoid replacement regimens are inadequate. In CAH, glucocorticoid doses that achieve androgen suppression are likely to induce hypertension, obesity, insulin resistance, and hyperglycaemia, even using hydrocortisone (cortisol). Preliminary data suggest, however, that the alternative glucocorticoid corticosterone is equally effective as cortisol in suppressing ACTH but is less potent than cortisol at inducing adverse metabolic effects. The researchers will test this hypothesis further. Positive proof-of-concept data will justify developing corticosterone as a novel treatment strategy to improve health outcomes for patients with CAH.
Investigator Dr R Stimson, Edimburg University, UK
Funding 60.000 euros
Project 4: Gene therapy, an option for severe cases of CAH
In the most severe form of CAH, marked androgen production during intra-uterine life, induces complete sexual ambiguity at birth.After surgical correction and despite careful medical treatment, the girl’s body and genitalia remain exposed to lifelong and severe chronic virilization that results in a major restriction of sexual and marital life in adulthood justifying new therapeutic intervention, potentially including gene therapy. This project aims at evaluating the efficacy of the process in animal models. It was previously funded through partnership with AFM. Encouraging results justified a prolongation of the funding.
Investigators: M Perdomini et P Bougnères, Le Kremlin_Bicêtre, France
Funding: 100.000 euros