02 May There’s finally some good news on endometriosis

 While there is still work to be done, we’re excited by the possibilities our new hydrogel opens up for identifying new non-hormonal treatments for endometriosis, which in the future, could benefit thousands of women, writes Dr Jacqueline Donoghue

Endometriosis is a common and painful gynaecological disease that impacts 14 per cent of women and girls across the world – currently, there is no long-term cure.

Finding new treatments for endometriosis is now more critical than ever.

The number of diagnoses is increasing each year as awareness of the disease grows, patient advocacy increases and diagnostic approaches improve.

Exploring alternative and non-invasive approaches to treating endometriosis may well be on many women’s minds following news of unnecessary surgeries and inappropriate medical treatments.

To test new therapies and medicines for treating endometriosis, we need tailored bioengineered hydrogels to test them in – that is, soft biomaterials that can accurately mimic how cells behave in the body.

Currently, testing treatments for endometriosis with existing hydrogels remains challenging. But, with the support of the Graeme Clarke Institute for Biomedical Engineering, we’re looking to change that.

Let’s start with the basics

Endometriosis is the growth of abnormal tissue or lesions in the abdominal cavity. These lesions have a similar appearance to the inner endometrial lining of the uterus, the same tissue that is expelled each month during menstruation.

These lesions are very responsive to estrogen, and over time, they can cause significant inflammation.

When they invade the surrounding organs like the ovary, colon or pelvic floor, patients can experience significant pain.

Treatment options can vary, from using pain relief medications like non-steroidal anti-inflammatories (NSAIDs), to hormone therapies that suppress ovulation/periods or surgery to remove endometriotic lesions and adhesions.

As endometriosis symptoms like chronic pain in young women are often dismissed, diagnosis can take an average of seven years and require surgical confirmation.

Unfortunately, current treatment options, including surgery, are not always curative.

Up to 50 per cent of patients relapse within five years, and over 90 per cent will also have co-morbidities like bowel lesions, pelvic adhesions or adenomyosis.

Hormone suppression has challenges too – it’s not viable long term due to impacts on conception and natural fertility, and for some medications, premature menopause and reduced bone density are significant risks.

This means that while surgery and hormonal interventions offer short-term relief, they are not optimal for long-term care and treatment of endometriosis.

This is why researchers are looking into alternative treatments and why testing them in the right environment – in this case, the right hydrogel – is so important.

The problem with current hydrogels

Traditionally, drug testing was performed on 2D flat surfaces that don’t fully replicate the biological environment.

This means that many drugs tested in the lab don’t always translate to the clinic. So cancer researchers developed 3D cellular structures to better mimic disease-specific environments.

While some cells grow freely inside these structures, others need extra material to hold onto, so they behave like they would inside real human tissue, which is where hydrogels come in.

Replicating biological systems in the lab using 3D hydrogels is now one of the best approaches for testing the potential of new drugs.

They help us to evaluate changes in cellular function and responses to treatments in a format that is very similar to the physiological or biological state.

When it comes to testing for endometriosis specifically, we also need a hydrogel that accurately represents the hormonal influence and inflammatory conditions of the disease.

Promising results

When biologists and bioengineers work together, amazing discoveries and major medical breakthroughs can happen – the merging of innovative ideas and technology is a wonderful thing.

In 2023, we tested more than 3500 already-approved drugs on endometrial cells to identify new non-hormonal drug therapeutics for endometriosis.

From this study, we identified 23 drugs that could be repurposed for endometriosis treatment, including those that reduced oestrogen-driven cell growth.

An important first step, with promising initial results.

In this instance however, the tests were conducted on a flat surface. So, it’s time to validate these findings in 3D to assess their real potential.

But first, we need to design the right hydrogel.

Initial findings of our ongoing project show endometrial cells are growing in our new hydrogel, just like they would under the usual physical conditions of endometriosis in the body – conditions like inflammation and hormonal influence.

As endometriosis is an invasive disease, it’s important that our cells replicate this invasiveness in the hydrogel. Our initial tests demonstrated this kind of cellular modification too – another important tick.

These findings provide early evidence that we now have the tools we need to push our drug screening even further.

Our hydrogel, cell type and environmental conditions are highly representative of the most severe forms of endometriosis.

The next part of this work will be to refine our model in a high-throughput screening process – an automated, rapid drug discovery process that allows us to test thousands of biological compounds to identify potential new drugs.

If finding potential new drugs is like looking for needles in a haystack – this method will be like using a magnet to find them.

From lab to clinic

Our work allows us to continue expanding our testing and improving current drug-screening methods for endometriosis, with the aim of overcoming the stubborn barrier between the lab and the clinic.

While there is still work to be done, this International Women’s Day – and Endometriosis Awareness Month – we’re excited by the possibilities our new hydrogel opens up for identifying new non-hormonal treatments for endometriosis, which in the future, could benefit thousands of women.