New Drug to Improve Fertility in Women With Reproductive Health Problems

Dawn O'Shea

November 20, 2020

A team of researchers led by Imperial College London have developed a new drug that can improve fertility in women with reproductive health problems, according to an article published in the Journal of Clinical Investigation.

The team conducted in vivo and in vitro studies to characterise the action of MVT-602 in comparison with native kisspeptin-54 (KP54). They determined the pharmacokinetic and pharmacodynamic properties of MVT-602 (doses 0.01 and 0.03 nmol/kg) versus KP54 (9.6 nmol/kg) in the follicular phase of healthy women (n=9) and in women with polycystic ovary syndrome (PCOS; n=6) or hypothalamic amenorrhoea (HA; n=6).

The study also investigated the effects of both MVT-602 and KP54 on KISS1R-mediated inositol monophosphate (IP1) and Ca2+ signalling in cell lines and on potential firing of gonadotropin-releasing hormone (GnRH) neurons in brain slices.

In healthy women, the amplitude of luteinizing hormone (LH) rise was similar to that after KP54, but peaked later (21.4 vs 4.7 hours; P=.0002), with correspondingly increased area under the curve of LH exposure (169.0 vs 38.5 IU∙h/L; P=.0058). LH increases following MVT-602 were similar in PCOS and healthy women but were higher in HA (P=.004).

MVT-602 induced more potent signalling of KISS1R-mediated IP1 accumulation and a longer duration of GnRH neuron firing than KP54 (115 vs 55 minutes; P=.0012).

Lead author, Dr Ali Abbara, consultant in endocrinology at Imperial College Healthcare NHS Trust, said: “This is the first study to show that a single dose of MVT-602 can induce a longer duration of hormonal stimulation in women than naturally occurring kisspeptin. Therefore, it reveals exciting potential to treat a range of reproductive health conditions using MVT-602 and offer women improved treatment options. However, further research is needed to fully characterise its effects in specific disorders that affect reproductive health.”

Abbara A, Eng PC, Phylactou M, Clarke SA, Richardson R, Sykes CM, Phumsatitpong C, Mills E, Modi M, Izzi-Engbeaya C, Papadopoulou D, Purugganan K, Jayasena CN, Webber L, Salim R, Owen B, Bech P, Comninos AN, McArdle CA, Voliotis M, Tsaneva-Atanasova K, Moenter S, Hanyaloglu A, Dhillo WS. Kisspeptin receptor agonist has therapeutic potential for female reproductive disorders. J Clin Invest. 2020 Nov 16 [Epub ahead of print]. doi: 10.1172/JCI139681. PMID: 33196464 View full text

This article originally appeared on Univadis, part of the Medscape Professional Network.

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