New local ganirelix sustained release therapy for uterine leiomyoma. Evaluation in a preclinical organ model

Currently, there is a limited number of treatment options available for patients with symptomatic leiomyomas, and surgical removal is by far the most frequent procedure. Previous studies found that GnRH agonists and antagonists acting through GnRH receptors led to cell death and decreased extracellular synthesis in cultured leiomyoma cells. In this study, we encapsulated the GnRH antagonist ganirelix in PLGA microspheres contained in an alginate scaffold that also supports a leiomyoma ex vivo tissue explant. Microspheres maintained ganirelix concentration stably during six days of culture, inducing significant cell death in 50-55% of tumor cells. Although no changes were observed in the expression of extracellular matrix genes, a decreased expression of the Nuclear Factor of Activated T cells 5, a transcription factor involved in osmotic stress and tumor size. Inter-estingly, all tumors analyzed experienced apoptosis independently of the original driver mutation. These data indicate that local therapy of ganirelix would induce tumor reduction in a wide range of uterine leiomyomas.

Automated summary

Currently, surgical removal is the most common treatment for symptomatic leiomyomas due to the limited treatment options available. Previous studies have shown that GnRH agonists and antagonists can induce cell death and decrease extracellular synthesis in leiomyoma cells. In this study, the GnRH antagonist ganirelix was encapsulated in PLGA microspheres and contained in an alginate scaffold, resulting in significant cell death in 50-55% of tumor cells. Although there were no changes in the expression of extracellular matrix genes, a transcription factor involved in osmotic stress and tumor size showed decreased expression. Interestingly, all tumors analyzed experienced apoptosis regardless of the original driver mutation. These findings suggest that local therapy with ganirelix could effectively reduce the size of uterine leiomyomas.