Tapeworm drug could help treat endometriosis, mouse study hints

A modified tapeworm medication could be a promising new treatment for endometriosis, an early study in mice hints.

In endometriosis, tissue similar to the lining of the uterus grows outside the organ, and these patches of tissue, called "lesions," trigger painful inflammation and heavy menstrual bleeding. In the new study, scientists fitted an anti-worm drug with nanotech armor, and it directly targeted these painful lesions in laboratory mice.

The treatment reduced inflammation and slowed or prevented further spread of the lesions, researchers reported in August in the journal Advanced Healthcare Materials. The team is already working on bringing the new drug to clinical trials and hopes this will bring fresh attention to an understudied disease with limited treatment options.

Rogue immune cells are a promising drug target

Endometriosis is a chronic, hormone-driven condition that affects roughly 10% of reproductive-age females ‪—‬ an estimated 190 million individuals worldwide. "The main symptoms are chronic pelvic pain and infertility," said Ioannis Simitsidellis, a postdoctoral researcher at the University of Edinburgh's Centres for Reproductive Health and Inflammation Research, who wasn't involved in the study.

There is currently no cure, so existing treatments aim to alleviate the symptoms. Hormonal medications can stall the menstrual cycle to limit the growth and inflammation of the lesions, while surgery can physically remove lesions. However, the former can come with side effects, such as nausea and mood swings, and lesions often regrow after surgery. So additional options are needed.

In previous research with mice, study co-author Kanako Hayashi, a professor in the Washington State University School of Molecular Biosciences, identified a group of rogue immune cells specific to endometrial lesion tissue. These cells turbocharged the painful inflammatory reactions and drove the growth of more of this problematic tissue.

The cells also happen to have a unique chemical label, called a folate receptor, which makes them an excellent potential drug target. But why start from scratch when there's an existing medication that might do the trick?

Enter niclosamide, a drug approved by the Food and Drug Administration to treat tapeworm infections. In recent years, clinicians have been exploring whether this medicine could also prove effective for other conditions, ranging from cancer to Parkinson's disease.

"We have reported that niclosamide inhibits endometriosis progression, suppressing the inflammatory mechanisms and cytokine secretions," said Hayashi, referencing more of the group's past work in mice. However, several issues made the drug impractical: It doesn't dissolve well in water, last long in the body, or target the cells where it's needed most.

So the researchers teamed up with Anjali Sharma, a nanomedicine specialist at the University of Michigan, to tweak the drug's structure. Using click chemistry — a simple reaction that bolts together two chemical building blocks — Sharma attached the niclosamide unit to a large, tree-like molecule called a dendrimer. This helped the drug dissolve better in blood.

She then added a folate group, which ensured that the modified medication would only target the rogue immune cells with the complementary receptor.

"The drug is attached in such a way that when it is in systemic circulation, nothing happens until it goes inside the diseased cells," Sharma said. Once there, it is slowly released inside the cell over a period of two weeks. "Basically, the dendrimer is like the Uber, the folate is like the GPS, and the drug is like the passenger," she explained.

The next steps

With these practical issues resolved, the team tested the modified drug in a mouse model, which mimics the lesions seen in endometriosis in humans. Scans of the mice showed that the treatment directly zeroed in on the affected endometrial tissue and didn't accumulate in other organs, like the liver.

Treating mice with a single injection dramatically reduced their pain symptoms, compared with untreated mice. It also slowed ‪—‬ or, in some cases, entirely halted ‪—‬ the growth of new lesions.

Because mice don't naturally menstruate or develop endometriosis, there is still significant work to do before these findings can be replicated in humans. But for now, the study is a promising stepping stone for future research, Simitsidellis said.

"There's a lot of potential in repurposing of drugs that have been tested in clinical trials to see if they would be effective in endometriosis ‪—‬ for example, targeting inflammation or immune cell dysfunction," he told Live Science. "The next steps would be to replicate on larger sample sizes and, if that's promising, do a phase one clinical trial in humans." That initial trial would test the treatment's safety in patients, while later trials would look at its effectiveness for endometriosis.

Even at this early stage, though, patients are clamoring to get involved in the upcoming research. Hayashi and Sharma have received hundreds of emails asking to join a future trial.

"They are really suffering," Hayashi said. "Endometriosis is an understudied, underacknowledged, underfunded disease, but hopefully we can make this a solution in the near future."