How a drug for TAPEWORM could end the crippling pain of endometriosis

A 60-year-old drug for tapeworm could banish endometriosis – the painful condition that affects about 1.5million women in the UK.

Niclosamide has been used for decades to kill the gut parasites, starving them to death by shutting off their supply of glucose, their main energy source. Now scientists in the US have developed a highly targeted version of the drug which, in animal tests, was able to shrink lesions in the abdomen formed when tissue that normally makes up the womb lining (the endometrium) spreads outside the organ.

This tissue can grow in the ovaries, bowel, bladder – even in some cases, the spine, lungs or brain – and behave just like womb tissue, swelling and bleeding every month during menstruation, causing inflammation, pain and a build-up of scar tissue in that area.

Bands of fibrous tissue, called adhesions, may also form, causing pelvic tissues and organs to stick to each other. Endometriosis is also one of the most common conditions linked to female infertility.

Poor awareness means it takes on average more than nine years for women to receive a diagnosis, according to the charity Endometriosis UK.

Current treatments range from over-the-counter painkillers, such as paracetamol or ibuprofen, to hormonal contraceptives (which regulate periods) or surgery to remove the excess tissue, or even – in the most severe examples – to remove the womb and the ovaries.

Niclosamide has emerged as a potential new treatment because studies show it can shut down major signalling pathways that control cell growth in a wide range of diseases.

For this reason, scientists around the world are investigating its potential in tackling kidney disease, Covid and diabetes.

The drug is also being investigated for use against a number of cancers – including bowel, brain, breast, prostate and lung cancer – as research suggests it causes the mitochondria (the ‘battery-pack’ inside all cells, including cancerous ones) to self-destruct.

Niclosamide does have a downside, however. Because it doesn’t dissolve easily in water, much of the oral medication currently used in tapeworm treatment does not find its way into the bloodstream and instead stays in the gut.

This means it does not reach the endometriosis lesions.

To overcome this problem, researchers at Washington State University created a type

of water-soluble, tree-shaped structure – called a dendrimer – that they impregnated with the active drug before injecting it into the body.

The dendrimer shape allows them to carry tiny drug molecules into the body.

This construction, too small to be seen with the naked eye, also contains folic acid – which binds to a protein found on the surface of immune cells, called FR-beta, which congregate in lesions and areas of inflammation.

Previous studies have shown that endometrial lesions have a high concentration of these FR-beta cells, which are thought to play a major role in the disease’s progression and chronic symptoms such as pain. Once the dendrimer has attached to these immune cells, it releases its drug payload straight into the cell.

Researchers tested the drug-laden scaffolding on mice engineered to have endometriosis – injecting it directly into the abdomen, close to the site of the lesions. Researchers gave the mice either a high dose of niclosamide or a low dose.

Results – published in the journal Advanced Healthcare Materials in August – showed that two weeks after treatment, four of the eight mice on the low dose and five of eight on the high dose had no detectable lesions, suggesting the endometriosis was cured.

They also had reduced sensitivity to pain and the benefits continued for at least two weeks.

Anjali Sharma, a member of the research team and an associate professor of pharmaceutical sciences at the University of Michigan, said of endometriosis: ‘One of the major challenges has been developing treatments that are both effective and safe for long-term use.

‘Our goal is to address the underlying disease pathology and ultimately improve the quality of life for millions of women.’

The hope is that the injectable tapeworm drug could eventually be given to women as a once-a-fortnight injection into the arm.

Once in the bloodstream, it would circulate around the body until it finds – and docks with – the FR-beta immune cells in the endometrial lesions.

Andrew Horne, a professor of gynaecology and reproductive sciences at the University of Edinburgh, said: ‘Targeting the immune system is a promising idea, and reusing an existing drug could, in principle, speed things up.

‘However, this study is a very early first step.’

He added that the main limitation was that it was done on mice, which don’t have periods and don’t naturally develop endometriosis.

This means there is no guarantee humans will respond in the same way. Professor Horne said: ‘The study was also small and short, lasting up to three weeks. Plus, it looked at endometriosis lesions and pain behaviour rather than long-term outcomes.

‘We don’t yet know whether the treatment is safe over months or years, how often it would need to be given – or whether it would work in people.’