Target Discovery in Endometriosis and Uterine Fibroids
The Oxford-Bayer Healthcare Alliance in Women's Health is a successful joint venture between several MSD Departments (currently NDWRH, NDORMS, and NDM) at Oxford University and Bayer Pharma AG, now in the 4th year of phase I of its operations. The remit of this partnership is to jointly validate targets, develop novel clinical drug candidates and promote understanding of disease biology in areas of unmet need in women's health such as endometriosis, uterine fibroids and polycystic ovary syndrome (PCOS).
Endometriosis is a potentially debilitating condition affecting 5-10% of women of reproductive age, where endometrial tissue is found in ectopic, mostly peritoneal locations, causing pain, infertility, fatigue and bowel or bladder problems. Many of the symptoms of endometriosis are driven by inflammation at the ectopic locations. Combining the knowledge base of both the University of Oxford and Bayer Healthcare, multiple projects are examining the roles of novel inflammatory mediators, where we have identified a potential role in endometriosis, with the aim of establishing new targets for therapy.
Uterine fibroids are benign tumours of the myometrial layers of the uterus with an incidence rate of >70% in women at age 50. The most common symptom of fibroids is heavy menstrual bleeding, which adversely affects quality of life via pain, anaemia, and mood swings. Although driver mutations in chromatin proteins MED12 or HMGA2 are found in the majority of fibroid occurrences, the mechanisms by which these mutations lead to fibroids and, by extension, to clinical consequences such as heavy menstrual bleeding, remain poorly understood. Leveraging the truly multidisciplinary expertise across the Nuffield Department of Women's & Reproductive Health, the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, the Nuffield Department of Medicine and Bayer, we are taking a system biology approach to identify the pathomechanisms of uterine fibroids. This information is being used to identify novel targets for the development of non-surgical treatments for uterine fibroids and associated symptoms.
Polycystic ovary syndrome (PCOS)
PCOS is an endocrine disorder characterised by a complex dysfunctional relationship between the neuroendocrine system, the female gonads and peripheral tissues such as adipose tissue or skin. Whereas genome-wide association studies (GWAS) and twin studies have highlighted the importance of the hypothalamic-pituitary-gonadal (HPG) axis and metabolic factors in PCOS, recent functional studies have revealed the critical importance of local hormone generation in adipocytes, driving and exacerbating metabolic phenotypes as observed in PCOS including insulin resistance.