Advancements in Fertility Treatment: The Emergence of a Novel Long-Acting Recombinant FSH Agonist

A new type of human follicle-stimulating hormone (FSH), called KN015, has been developed and is being studied for its potential as a clinical treatment. KN015 is a fusion protein made up of FSHα and FSHβ-Fc/Fc and has been found to have a longer half-life and higher bioactivity in vivo compared to existing recombinant human FSH (rhFSH). This longer-lasting FSH could be a promising alternative for clinical use.

The study conducted experiments to produce KN015 using Chinese hamster ovary cells and then evaluated its pharmacokinetics in rats and monkeys. The purity and molecular weight were determined through gel electrophoresis, and the half-life was measured by collecting serum samples at various times and analyzing the remaining FSH concentration.

In vitro tests were performed to compare the bioactivity of KN015 with rhFSH. This included assessing cAMP production in CHO cells with FSH receptors and observing the effects on cumulus oocyte complexes in mice. The in vivo activity was compared by measuring ovary weight gain and ovulation rates in rats.

The results showed that KN015 has a molecular weight of 82 kD and a significantly longer half-life than rhFSH, with 84 hours in rats and 215 hours in monkeys. It was also found to be more effective in stimulating ovary weight gain and had a higher serum estradiol level compared to rhFSH. Furthermore, KN015 induced target genes and activated the PI3K pathway more effectively than rhFSH.

However, the study acknowledges that all assays were conducted in animals, and clinical trials are necessary to determine the applicability to humans. The research was funded by the National Basic Research Program of China and the National Natural Science Foundation of China, with no conflicts of interest reported by the authors. KN015 is considered a valuable alternative to FSH with significant potential for therapeutic use.