Everything is accelerating for endometriosis. The fight against this gynecological disease which affects 10% of women – in France around 2 million people – has been the subject of of a national strategy, launched by Emmanuel Macron. The first meeting of its steering committee took place on Monday. One of the priority objectives is to better diagnose it. Currently, women live an average of eight years of “medical wandering” before making a diagnosis of this disease, a source of severe pain (digestive disorders, lesions, cysts, etc.) and sometimes even infertility.
It is in this rich context that Ziwig intervenes. This start-up from Lyon has just developed a test for detecting the disease – the “endotest” – from a simple saliva sample. Presented on Friday, this screening is based “on high-throughput sequencing of microRNAs present in saliva and on the use of artificial intelligence to process the very large volume of data thus generated”, we explain. at Ziwig. Its result, obtained in about ten days, would be “a performance superior to that of all the diagnostic tools currently available (laparoscopy, MRI, pelvic ultrasound)”, boasts the start-up. The test would also be reliable in almost 100% of cases, with a risk of false positives almost zero.
“As a practitioner, we had dreamed of this for years,” commented Philippe Descamps, head of the obstetrics gynecology department at the Angers University Hospital, who collaborated on its design with several experts from the National College of French Gynecologists and Obstetricians. The artist Imany, ambassador of the Endomind association, thus hailed on Twitter a “huge victory”. Yes but here it is. Other players remain cautious about the emergence of this screening. Quite rightly so.
New expected results
First, it should be noted that the device is not yet marketed. He is waiting in France for the green light from the High Authority for Health (HAS), in particular with a view to reimbursement by Medicare, decisive for a massive deployment. But the process might take a little time. Because the study which currently confirms the “endotest”, carried out on 200 women (including 153 for whom endometriosis has been officially diagnosed), and published in the Journal of Clinical Medicine, has its limitations. The first: with the same cohort, this made it possible not only to determine the 109 microRNAs present in the saliva from people suffering from endometriosis, but also – and this is more problematic – to evaluate the effectiveness of the test.
This is why another study, called multicentric, is currently at work on nearly 1000 other women, whose saliva is collected from the four corners of France. Questioned on the question, Monday, the Minister of Health Olivier Véran himself insisted on the fact of “consolidating the data on a much larger cohort”. A sign of “cautious optimism”, the EndoFrance association, which does not even relay the news on its social networks, also tells L’Express to wait for the conclusions of this second study and “the validation of the health authorities”, before to speak out officially on the subject.
How long can this process take? “The trial is already underway,” reports Gilles Doumer, vice-president of Ziwig, to L’Express. Is it therefore a matter of several weeks? Months? Hard to say. The HAS will probably ask for the detailed results of this multicenter study before making a decision. The process with the health authorities will be “long and complex” recognizes Gilles Doumer. Ziwig is however very confident. “We are sure to have developed a discriminating and reliable test, thanks to our algorithms”, insists the leader of the start-up. Why, then, rush its communication? “Because we are ready. If tomorrow an order comes from a foreign country, we have no production or implementation constraints.”
Concretely, the creators of the endotest want above all to take advantage of the strong media coverage of endometriosis to push the authorities to go even faster. “The Covid crisis has shown that we can quickly provide patients with tests if we consider that it is an emergency situation (…) For all these specialists in this gynecological disease, there is no no doubt that this test will one day be available and reimbursed”, estimates Philippe Descamps, from the CHU of Angers, with our colleagues from 20 minutes.
A still recent field of research
This urgency would also explain why the results of this study – major for the health of women across the planet, not only in France – were published by MDPI, a publisher – hosting the Journal of Clinical Medicine – more and more decried for its “predatory” methods: massive, expedited proofreading, with in addition high publication costs, sometimes of the order of several thousand euros. “The review isn’t bad, but it’s not the New England Journal of Medicine or even the Lancet, supports the geneticist and biologist of reproduction, director of research at Inserm, Daniel Vaiman. The process of reviewing (replay) would then have been much meaner, and probably would have demanded more results.”
“The Lancet and the New England are not reputed to publish on breakthrough innovations”, defends Gilles Doumer, who slays the critics who came to enamel the announcement of the endotest. “It’s a bit like the enlightened experts who said that Pfizer-BioNTech was unable to make a vaccine against Covid-19 in a year …”, he breathes, while announcing other publications, on the same subject and by the same teams, to come in the – more listed – review Nature.
But unlike messenger RNA, used for these vaccines, the literature around microRNAs is less abundant: about 350 articles since the early 2000s, according to Daniel Vaiman. Succeed in identifying, what is more in the saliva, these biomarkers likely to ensure the presence of endometriosis is a real achievement. “Micro-RNAs generally come from degradation of target tissues. For example, we find a lot of them in the blood after a heart attack, explains the scientist. In a chronic disease, which extends over several years such as endometriosis, there is no There is no sudden damage to a tissue. Finding microRNAs is therefore a challenge.” Ziwig’s success could be explained by a change in approach consisting of looking for all the microRNAs identified in research and identifying in patients suffering from endometriosis which ones came back most commonly, thanks to the help of an intelligence artificial. But the method does not convince everyone.
“This is more marketing than science”, thunders in particular on his Twitter account a biologist at the CNRS, who intends to remain anonymous. In private, she develops somewhat: “Almost any biologist will tell you that an endometriosis marker in saliva sounds like a joke.”
“Limits Series”
Outside the study, Daniel Vaiman remains moderate: “There is no reason to doubt the results found”. The biologist, on the other hand, points to several questions, still outstanding: will the test be effective in recognizing early cases in adolescents (not included in the first cohort)? Will it be able to detect all types of endometriosis? “Another problem: could other chronic diseases give microRNA profiles similar to those found and falsify the results?”, he finally wonders. A “series of limitations” which, in addition to the ongoing multicenter study, make the production of an effective kit unlikely in the short term, according to him.
This is more or less the speech held by his colleagues. Quoted by Le Figaro, Professor Chérif Akladios, head of the obstetrics gynecology department at the Hautepierre hospital in Strasbourg, also judges Ziwig’s first results “promising”, obviously awaiting more information. But it already diminishes its scope. “Is it used as soon as you suspect endometriosis? Personally, I would like to use it when the MRI of a patient who complains of pain comes back negative. This allows you to add a step before laparoscopy, which has good results but remains an invasive examination, requiring general anesthesia”, he explains.
Detecting endometriosis as we detect Covid-19 today is not for tomorrow. And if, in the end, the endotest was not reimbursed by Social Security? Asked about the real price of sequencing, Gilles Doumer kicks in touch, judging much higher the “5000 euros” generally spent by patients, after several years of medical appointments and examinations to identify endometriosis.