New drug can improve fertility in women with reproductive health problems

A drug that acts via the natural ‘kisspeptin’ hormone system in the body has the potential to treat reproductive health problems in women, according to a new study.

Twenty-four women were injected with a drug called MVT-602 which targets the kisspeptin system to stimulate reproductive hormones that affect fertility, sexual development and menstruation.

The naturally occurring form of kisspeptin called kisspeptin-54 (KP54) has been researched for a number of years to treat reproductive disorders, but in the new study, MVT-602 induced more potent signalling of the kisspeptin system over a longer period of time than KP54.

The researchers behind the study suggest that MVT-602 may be used to effectively treat a range of reproductive conditions that affect fertility such as polycystic ovary syndrome (PCOS) – a common condition that affects how a woman’s ovaries work and hypothalamic amenorrhea (HA) – a condition where a woman’s periods stop.

The researchers suggest that because of MVT-602’s much longer duration of action, it can be given less frequently than the naturally occurring form of kisspeptin, whilst still being able to maintain the degree of stimulation of reproductive hormone levels required to restore reproductive health.

The study, published in the

Journal of Clinical Investigation

, is led by researchers at Imperial College London and clinicians at Imperial College Healthcare NHS Trust.

Professor Waljit Dhillo, lead author, NIHR Research Professor in Endocrinology and Metabolism at Imperial College London and Consultant in Endocrinology at Imperial College Healthcare NHS Trust said:

“Reproductive health issues are common for women around the world. Infertility as a result of these conditions can cause a lot of distress. Although we have made great strides in developing treatments for infertility and other reproductive disorders there is a need to find more effective treatments. Our previous work showed that kisspeptin can be used to stimulate ovulation in women undergoing in vitro fertilisation (IVF) treatment, but there are some limitations on using the naturally occurring kisspeptin hormone as its effectiveness wares off after a few hours. 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. This is an early stage study and more research needs to be carried out to fully determine the effects of MVT-602 on more patients.”

Dr Ali Abbara, NIHR Clinician Scientist at Imperial College London and Consultant in Endocrinology at Imperial College Healthcare NHS Trust, who co-led the work added: “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.”

One in ten women in the UK are diagnosed with PCOS or HA. Current treatments for these conditions include dietary changes, medicines that treat infertility by restoring ovulation, and IVF treatment for those who still are unable to conceive. However, women with PCOS who undergo IVF treatment are at increased risk of ‘ovarian hyperstimulation syndrome’ (OHSS) – a potentially life-threatening side-effect of IVF treatment.

Kisspeptin is a naturally occurring hormone that controls the levels of other reproductive hormones in the body and plays an important role in fertility, reproductive health and the regulation of normal menstrual cycles. Previous studies have shown that kisspeptin can be used to safely stimulate reproductive hormones in women undergoing IVF treatment without causing OHSS. The research team wanted to see whether MVT-602 could target the kisspeptin pathway and produce a longer hormonal release than the naturally occurring form of kisspeptin – which is important for using kisspeptin to treat reproductive disorders.

Researchers carried out a trial at Hammersmith Hospital, part of Imperial College Healthcare NHS Trust, on 24 women aged 18-35 from 2017-2019. Twelve of the women were healthy volunteers and 12 of the women had either PCOS or HA. All of the women were given MVT-602. 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.

They found that all of the women given MVT-602 had a longer duration of raised reproductive hormones, specifically luteinising hormone (LH) and follicle stimulating hormone (FSH) levels, than when they received native kisspeptin (KP54). LH levels peaked at 21-22 hours after MVT-602 and remained elevated for 48 hours. This is in comparison to natural kisspeptin (KP54) whereby LH levels peaked at 4.7 hours after administration and remained elevated for 12-14 hours. Therefore, the duration of LH rise was extended by approximately four times using MVT-602.
LH increases following MVT-602 were similar in PCOS and healthy women, but rose more quickly in women in HA. Theoretically, this could be because women with HA have more kisspeptin receptors in the hypothalamus of the brain where kisspeptin acts as a result of their condition.

The researchers will now aim to carry out further studies on the effects of MVT-602 on women with reproductive disorders.

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The study was funded by NIHR Imperial Biomedical Research Centre (BRC) and an NIHR Professorship & Clinician Scientist Awards.

More information about participating in future research studies using kisspeptin can be reached by contacting

[email protected]

.

For further information, please contact


Maxine Myers

AHSC Communications Manager

Imperial College London

Tel: +44 (0) 7561 451724

Email:

[email protected]

Duty press officer mobile:


+44 (0) 7803 886248

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Notes to Editors

1. About Imperial College Academic Health Science Centre

The AHSC is a partnership between Imperial College London, The Institute of Cancer Research (ICR) Imperial College Healthcare NHS Trust, Royal Brompton & Harefield NHS Foundation Trust, Chelsea and Westminster NHS Foundation Trust and the Royal Marsden NHS Foundation Trust, based in West London.

Established in 2007, it was the first AHSC to be created in the UK and was formally designated by the Department of Health in 2009.

The partnership brings together multi-disciplinary research and education from across all faculties at the College with the resources and critical mass of the three Trusts to advance discovery and innovation within healthcare.

The purpose of Imperial College AHSC is to utilise excellence in research and education to transform health outcomes, and support the UK’s globally competitive position in healthcare related industries by increasing societal and economic gain.

The AHSC is nested within Imperial College Health Partners, the Academic Health Science Network for North West London, which will ensure that discoveries and innovations are applied on a national and global scale.

2. About Imperial College London

Imperial College London is one of the world’s leading universities. The College’s 16,000 students and 8,000 staff are expanding the frontiers of knowledge in science, medicine, engineering and business, and translating their discoveries into benefits for society.

Founded in 1907, Imperial builds on a distinguished past – having pioneered penicillin, holography and fibre optics – to shape the future. Imperial researchers work across disciplines to improve health and wellbeing, understand the natural world, engineer novel solutions and lead the data revolution. This blend of academic excellence and its real-world application feeds into Imperial’s exceptional learning environment, where students participate in research to push the limits of their degrees.

Imperial collaborates widely to achieve greater impact. It works with the NHS to improve healthcare in west London, is a leading partner in research and education within the European Union, and is the UK’s number one research collaborator with China.

Imperial has nine London campuses, including its White City Campus: a research and innovation centre that is in its initial stages of development in west London. At White City, researchers, businesses and higher education partners will co-locate to create value from ideas on a global scale.

Imperial College London is a world-class university with a mission to benefit society through excellence in science, engineering, medicine and business.


http://www.

imperial.

ac.

uk

3. About Imperial College Healthcare NHS Trust

Imperial College Healthcare NHS Trust is one of the largest hospital Trust’s in England, providing acute and specialist healthcare for a population of nearly two million people. The Trust has five hospitals – Charing Cross, Hammersmith, Queen Charlotte’s & Chelsea, St Mary’s and The Western Eye as well as community services.

4. About the National Institute for Health Research (NIHR) is the nation’s largest funder of health and care research.

• Funds, supports and delivers high quality research that benefits the NHS, public health and social care.
• Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research. Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future.
• Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services.
• Partners with other public funders, charities and industry to maximise the value of research to patients and the economy.

The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. ‘In addition to its national role, the NIHR supports applied health research for the direct and primary benefit of people in low- and middle-income countries, using UK aid from the UK government