A new drug that may be able to improve fertility for women with ovulatory problems has been showcased by researchers at Imperial College London.
The drug, called MVT-602, acts via the natural ‘kisspeptin‘ hormone system in the body. It modifies the activity of kisspeptin, making it more potent, stable and water-soluble.
Kisspeptin is an important reproductive hormone involved in the release of two other hormones from the pituitary gland – luteinizing hormone (LH) and follicle stimulating hormone (FSH) – that regulate maturation and release of egg cells.
‘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,’ said study author Dr Ali Abbara, National Institute for Health Research (NIHR) clinician scientist at Imperial College London. ‘Therefore, it reveals exciting potential to treat a range of reproductive health conditions using MVT-602 and offer women improved treatment options.’
Researchers carried out a trial at Hammersmith Hospital, part of Imperial College Healthcare NHS Trust, on 24 women aged 18-35 from 2017-2019. They were injected with the drug and their levels of LH and FSH were measured over several days.
Twelve of the women had no ovulatory problems; six had hypothalamic amenorrhea (HA), characterised by a lack of ovulation; and six had polycystic ovarian syndrome (PCOS), an endocrine disorder which presents with enlarged ovaries and irregular periods.
In addition, all of the healthy volunteers were given an injection of the naturally occurring kisspeptin (KP54) and saline placebo for comparison. The researchers then compared the women’s reproductive hormone levels after receiving MVT-602 to naturally occurring kisspeptin (KP54). They also compared the reproductive hormone levels after MVT-602 between healthy women, women with HA and those with PCOS.
The drug was able to stimulate a similar LH peak to kisspeptin alone in all groups, but showed a longer duration of action – with the peak remaining high for an extended time. A particularly strong response was observed in women with HA.
Previous work has shown that the naturally occurring form of kisspeptin-54 (KP54) is able to stimulate ovarian function for IVF treatment, without increasing the risk of ovarian hyperstimulation syndrome (OHSS).
However, the effect of kisspeptin is short-lasting and frequent administration reduces its effectiveness, limiting its applicability.
MVT-602 induced more potent signalling of the kisspeptin system over a longer period of time than KP54, according to researchers.
‘Our previous work showed that kisspeptin can be used to stimulate ovulation in women undergoing IVF treatment, but there are some limitations on using the naturally occurring kisspeptin hormone as its effectiveness wares off after a few hours,’ said lead author Professor Waljit Dhillo, research professor in endocrinology and metabolism at Imperial College London. ‘This study suggests that MVT-602 can stimulate kisspeptin over a longer period of time with no side effects, which means we could potentially use it to treat a wider range of reproductive disorders.
The researchers suggest that MVT-602 may be used to effectively treat a range of reproductive conditions that affect fertility such as polycystic ovary syndrome and hypothalamic amenorrhea.
Though promising, the findings are very early and experimental, far away from being used in clinical practice to help subfertile women with ovulatory problems.
Read more: https://www.jci.org/articles/view/139681