Successes and failures of uterine leiomyoma drug discovery

Introduction: To-date, the only cure for symptomatic uterine fibroids (UFs) is surgical intervention. However, surgery may eliminate the hope of future pregnancies; moreover, the intrinsic risks of surgery make it a less favorable to women with UFs. Because of this, conservative medical therapies have become an attractive and prior option for those women. Leuprolide acetate (LA), a gonadotropin-releasing hormone (GnRH) agonist, is the only pharmacological agent currently approved for the short-term and pre-operative management of symptomatic UFs in the USA.

Areas covered: This systematic review covers the successes and failures of prominent drugs that have been researched for UFs in the past and agents that have shown promise in recent clinical trials. The most recent clinical trials and advances in drug therapy are presented in a comprehensive overview outlining the direction UF drug discovery is heading.

Expert opinion: Experts in the field are already on the forefront leading the responsibility to uncover potential drugs as long term fertility friendly viable options for non-invasive treatment/prevention of UFs. Indeed, a shift in the UF management is expected in the future.     

Pharmacological treatment options for severe hypertriglyceridemia and familial chylomicronemia syndrome

Introduction: A spectrum of disorders, ranging from rare severe cases of homozygous null lipoprotein lipase deficiency (LPLD)–familial chylomicronemia syndrome (FCS) to heterozygous missense LPLD or polygenic causes, result in hypertriglyceridemia and pancreatitis. The effects of mutations are exacerbated by environmental factors such as diet, pregnancy, and insulin resistance.

Areas covered: In this review, authors discuss chronic treatment of FCS by ultra-low fat diets allied with the use of fibrates, omega-3 fatty acids, niacin, statins, and insulin-sensitizing therapies depending on the extent of residual lipoprotein lipase (LPL) activity; novel therapies in development target triglyceride (TG)-rich lipoprotein particle clearance. Previously, a gene therapy approach to LPL-alipogene tiparvovec showed that direct targeting of LPL function reduced pancreatitis events. An antisense oligonucleotide to apolipoprotein-C3, volanesorsen has been shown to decrease TGs by 70–80% and possibly to reduce rates of pancreatitis admissions. Studies are underway to validate its long-term efficacy and safety. Other approaches investigating the role of LPL modulating proteins such as angiopoietin-like petide-3 (ANGPTL3) are under consideration.

Expert opinion: Current therapeutic options are not sufficient for management of many cases of FCS. The availability of antisense anti-apoC3 therapies and, in the future, ANGPTL3 therapies may remedy this.