The French startup is revolutionizing the early diagnosis of endometriosis

A condition that affects an estimated 190 million women and girls worldwide, according to the World Health Organization, endometriosis is a difficult-to-treat chronic disease that causes debilitating pelvic pain. Often misdiagnosed as irritable bowel syndrome (IBS) and sometimes disbanded as menstrual cramps, diagnosis endometriosis can take about 10 years, increasing the severity of the condition. But this is bound to change as French startup Ziwig has found a way to diagnose this disease in 10 days.

Based in the city of Lyon, Ziwig, a biotech founded in 2019, aims to drastically cut the delay in diagnosis for people with endometriosis in order to receive the treatment they need as early as possible with the help of a saliva test.

What makes endometriosis so difficult to diagnose?

When tissue similar to that found in the uterine lining grows outside the uterus, affecting the ovaries, fallopian tubes, and pelvis, it is characterized by intense pain during sex and menstruation. This is because tissue such as the endometrium, which thickens and bleeds with each menstrual cycle, instead of being shed, becomes trapped in the ovaries, sometimes causing cysts to form. This in turn causes inflammation and scar tissue buildup, which causes pelvic pain and increases the risk of infertility.

While these symptoms may be indicative of endometriosis, it is still not easy to diagnose this disease. According to Andrew Spiers, head of Clinical Innovation at Ziwig, current diagnostics include filling out a patient’s symptom questionnaire. Spiers claims that while it is important to take a patient’s history, it is not specific enough to diagnose the condition.

One way to detect unusual tissue growth is through magnetic resonance imaging (MRI) scans and ultrasound. However, if the tissue is small and forms on the surface of the organ and not inside it, the scan may not detect it. Though, according to European guidelines, a negative result from a scan does not rule out the disease.

That leaves many people with the option of undergoing surgical procedures such as laparoscopy. This involves using a camera inside the abdomen where the inside of the intestines and pelvis is passed on to a screen to detect tissue such as the endometrium. While this can serve as a diagnostic tool for endometriosis, many avoid surgery because it is “a very invasive process,” explains Spiers.

How does the Ziwig Endotest work?

This is where the Ziwig saliva-based endometriosis test comes in. People are required to spit into a tube which is sent to a laboratory which will test for endometriosis. This is done by examining the microRNA in a saliva sample.

MicroRNAs (miRNAs) are short, single-stranded nucleotides involved in regulating gene expression. This links to messenger RNA (mRNA) – which has attracted attention in the Covid vaccine – to silence the gene, meaning that the proteins normally produced by mRNA, will no longer be produced.

After evaluating more than 2,600 miRNAs in patients, Ziwig was able to design a 109 miRNA signature that leveraged the capabilities of artificial intelligence. In a Study published in The New England Journal of Medicine last month, found that Ziwig’s Endotest, which assesses the saliva of women between the ages of 18 and 43, exhibits a sensitivity and specificity of over 95%. Additionally, it was validated in one of the largest clinical trials for endometriosis, in a whole hospital in France, and was also found to work well at room temperature.

“One of the main advantages of the Endotest is that it can replace diagnostic laparoscopy,” says Spiers. “And then they (patients) won’t be able to do invasive work and are better off doing an Endotest… There’s a long delay between when a practitioner does the imaging and then they might try probabilistic, what we call empiric treatment, to see if it helps. . And in some cases, patients do not want to undergo hormonal treatment without a diagnosis. And that is something very understandable. So it also gives the practitioner the possibility to provide the patient with a diagnosis before giving the drug that the patient has to take.

Because the Endotest is a prescription diagnostic tool rather than a screening method, it is recommended for use after imaging has been performed, according to practitioners.

“We feel that patients should have a clinical examination with a practitioner who will look for signs and symptoms of disease, and they should have imaging – either an ultrasound or an MRI. And if, after this, there is a very clear diagnosis, there is endometriosis, then the practitioner can continue treatment. Unfortunately, in the vast majority of imaging cases, there is no clear diagnosis,” Spiers said, noting that the reliability of the test can overcome problems around delays in diagnosis, and patients can know once and for all whether they have endometriosis, and then proceed with therapy.

Another shortcoming of current diagnostic measures that Endotest aims to address is the inability of other tests to accurately detect all forms of the disease. For example, there are times when laparoscopic surgery does not take the initial stage as well as the superficial peritoneal form of endometriosis, which is the most common type of the disease as it accounts for 80% of all endometriosis diagnoses. It is formed by the development of superficial lesions along the peritoneum, which is the membrane that lines the stomach. Other types of endometriosis include endometriomas – which are caused by cysts on the ovaries – and deep endometriosis – which burrow deep into the organs, attacking them.

Occasionally, in cases of superficial endometriosis, the surgeon may take a sample that may be only a few centimeters from the lesion site. So the Ziwig test is designed to address these issues with improved accuracy compared to other diagnostic tools.

“Endometriomas can be found reliably using pelvic ultrasound, whereas superficial disease is much more difficult to find. So again, the complexity of the disease adds to the difficulty of diagnosis. And, in some cases, imaging is sufficient and that’s why we say that patients should follow this path of having imaging. But, again, unfortunately, most of the time, it’s not enough to get a definitive diagnosis,” said Spiers.

Endometriosis treatment: need for faster diagnosis

Because patients are sometimes offered treatment without getting a formal diagnosis, Spiers explains that Endotest can give a definitive answer whether or not they have endometriosis.

“Patients who have symptoms, they don’t know what’s going on. In some cases, they have been given treatment empirically, they have been given treatment without a diagnosis. In fact, the diagnosis of Endotest, it gives answers to patients… If they don’t want to do empirical treatment, it means that a practitioner can give them treatment with the diagnosis that has been done. It also means that treatment pathways can be adapted very, very quickly, in the early stages, to help patients because the goal of treatment is to stop the disease from progressing. So, that actually means if we catch the disease early, we can stop it developing into end-stage disease.”

Although there is no known cure, some of the symptoms of endometriosis can be treated, especially if caught early. Many people are prescribed hormone therapy – namely the contraceptive pill – to stop the production of estrogen in the body because it stimulates the growth of endometriosis tissue. Surgery is also performed to destroy tissue to relieve symptoms.

Ziwig’s plans for the future

Currently available in parts of Europe such as the UK, Italy, Germany, Switzerland, as well as in Saudi Arabia and the United Arab Emirates, Endotest will soon be commercialized in Hungary, Belgium, Luxembourg, Kuwait, Qatar and Israel. In addition, the company is developing tests that can tell what type of endometriosis a patient has, as Ziwig focuses on expanding diagnostic options for all forms of endometriosis.

“This will be the first step towards developing truly personalized care. Because if we know exactly what biologic subtype a patient has, we can relate how these biologic subtypes respond to different treatment regimens. So, patients will have not only a diagnosis, but also indicators of the optimal treatment path for them. So this is going to be a tremendous added value,” said Spiers.

While endometriosis has become a understudied and underfunded disease over the years, Spiers relates that things are getting better now. “So endometriosis has, over the years, I think in some ways, been under-researched. And today, we’re seeing more and more research being done, and it’s incredible. I would say that research is definitely accelerating in the field and what needs to be done is being done, but again, we need to find treatment solutions that are targeted and personalized for patients.

Because it affects them from their teens until around menopause, endometriosis can change a patient’s life, according to Spiers.

“This is a disease that has a major impact on the patient’s quality of life. The symptoms are most acute at a time when they are making decisions for their studies, for their personal lives, for their professional lives,” said Spiers. “And when patients describe the pain, they describe it as very intense. So Endotest has great potential to help patients because currently, the average diagnostic delay between when a patient starts experiencing symptoms and when a diagnosis is reached, is many years. In some countries, five years, in some countries, 10 to 12 years. So, we basically reduced the diagnostic delay from 10 years to 10 days. And this means suffering patients can get customized care. And this is very important for us.”