Pre-clinical development of a blocking anti-Müllerian hormone antibody to treat the polycystic ovary syndrome – HAPY

The polycystic ovary syndrome (PCOS), the main cause of women infertility, associates reproductive and metabolic disorders. The daughters of women with PCOS mainly suffer from the clinical signs of hyperandrogenism. The treatments of adult and adolescent women with PCOS, are only symptomatic and can induce dangerous side effects. Cumulative evidence suggests that the high levels of Anti-Müllerian hormone (AMH) in women with PCOS are involved in their ovulation defects and likely also in the transmission of the syndrome to their children, through androgenization of fetuses during gestation. The consortium, constituted by researchers and physicians experts in reproduction and metabolism, has identified the first spontaneous rodent model of PCOS which displays all the reproductive and metabolic traits of this syndrome, the Goto-Kakizaki rats. Moreover, new results have shown that a blocking antibody against AMH, patented and supported by Inserm transfert (two Proof of Concept grants), rescues both ovulation and normal androgen levels in these rats. The main objectives of HAPY project are thus 1/ to optimize the protocol used to obtain these results in anovulatory adult GK rats, 2/ to adapt the protocol for adolescent GK rats, 3/ to test whether the treatment of anovulatory GK with the blocking anti-AMH can prevent the development of PCOS traits in their female offspring, and the molecular defects of their oocytes and 4/ to test whether this antibody can reverse the ovulation defects observed in a mono-ovular model of PCOS: androgenized sheep. Information on the issues addressed by HAPY should allow propose a new therapeutic target to treat patients with PCOS and to prevent the transmission of this syndrome to their descendants.