Finally hope against endometriosis? Researchers from the Japanese pharmaceutical laboratory Chugai published a promising study earlier this year in the review Science Translational Medicine. They administered an antibody to female macaques that reduced the lesions typical of the disease by half. A phase I clinical trial is underway in Japan and Taiwan. “We must evaluate the side effects on humans, but there is a good chance that this treatment will work”, rejoices Daniel Vaiman, research director at Inserm (National Institute of Health and Medical Research) .
A real plague of modern times, endometriosis affects at least two million women in France. A figure probably underestimated, because this pathology identified in 1927 remains difficult to diagnose. A chronic inflammatory gynecological disease, it is defined by the abnormal presence, outside the uterine cavity, of tissue similar to that of the endometrium (the lining of the uterus). Concretely, menstruation goes towards the interior of the body and not towards the exterior. They settle on organs such as the peritoneum, ovaries, bladder, digestive tract or vagina. This can cause inflammation and generate very strong pain. On a scale of 1 to 10, some patients report being at 10as much as for a delivery without an epidural.
“The most unbearable thing is not being able to move. At the slightest movement, I had the impression that a sword was piercing me”, testifies Arounie Tavenet, 37 years old. The ordeal of this Nancy began with her first period. First cramps, then increasingly strong digestive pains. “My belly was swelling, I was regularly asked if I was pregnant,” she recalls. It took him six years to finally get a diagnosis. During this time, the disease had had time to cause “a huge 5 centimeter cyst on an ovary”, removed by laparoscopy. The young woman will then begin hormonal treatment: it reduces the pain, but does not reduce the lesions… and prevents having children. “The side effects of the pill are significant, and the effectiveness is not always there. Doctors complete the prescription with painkillers, antidepressants… Some recognize that they are ‘cooking'”, laments Yasmine Candau, president of the EndoFrance association.
“The laboratories have broken their teeth on this disease”
The disease is difficult to grasp. Some women have significant lesions but feel no pain. Conversely, others suffer enormously while their lesions are limited. “Endometriosis can ruin the lives of some patients, but medical research has not fully invested in understanding this pathology which is not fatal”, regrets Daniel Vaiman. “In France, the results of research are still incomplete, and an insufficient number of teams are involved”, recognizes the Ministry of Health. A deficiency all the more astonishing as endometriosis has everything of an El Dorado for the pharmaceutical industry, given the number of patients. “The laboratories worked on it ten years ago, but broke their teeth, because it is a complicated pathology”, says Cécile Real, CEO of the company Endodiag.
Scientists are now trying to make up for lost time. The team of Marina Kvaskoff, epidemiologist at Inserm, organized a cohort of 60,000 patients. “Our study highlights three major expectations: improving knowledge and recognition of endometriosis among caregivers; putting an end to medical violence, in particular the paternalistic discourse of certain doctors, and, of course, improving care”, lists the scientist.
At the Cochin Institute, a biomedical research center located in the heart of Paris, a team supervised by Daniel Vaiman is trying to identify the genes involved in endometriosis, by comparing the genome of sick and non-sick women. For this, the researchers collected, by saliva sample or blood test, the DNA of 35 participants from ten different families. High-throughput sequencing of the coding parts of the genome should make it possible to determine the probability of having the pathology. Because heredity plays a role. “If a woman is a carrier of endometriosis, her daughter is five times more likely to be affected,” says Yasmine Candau. A large study published in March in Nature Genetics, in collaboration with the Californian biotech 23andMe, studied 70,000 women suffering from endometriosis and 700,000 control individuals: 42 positions on the genome correlated with the disease have already been discovered. “But this work comes up against two difficulties: the endometriosis group is very heterogeneous, and the control group is not necessarily reliable, because a patient can be affected by the disease without knowing it”, notes Daniel Vaiman.
Technology at the service of treatment
Also in Cochin, another team collects blood from menstruation to create “organoids“, 3D mini-uteri, in order to search for potential biomarkers, and treatment pathways. “Menstrual reflux affects many women, but some do not develop endometriosis. Scientists are therefore trying to see if something in the endometrium can explain the disease”, reports Julie Tabiasco, researcher in immunology in Toulouse. Like the Japanese scientists from the Chugai laboratory, this specialist puts on the track of immunity to provide an answer to patients. She is working on a means of remedying the dysregulation of the immune system characteristic of endometriosis. Her team has identified a target molecule which makes it possible to “wake up” our defenses with, as the key, “a reduction in 50% of the weight and volume of the lesions”, explains Julie Tabiasco. If this treatment proves to be effective in humans, it is in a way the patient’s body which will be its own medicine.
In the meantime, the other major research challenge remains to develop tools to facilitate the diagnosis of the disease. The symptoms can be trivialized (“it is normal to have pain when you have your period”) or confused with other conditions, women often go through a long period of medical wandering – seven years on average in France, according to the Ministry of Health. Created in 2019, the Lyon-based start-up Ziwig has developed a saliva test to remedy this. Its Endotest is based on the sequencing of micro-RNAs present in saliva, specific to affected women. He was the subject of a study published in January 2022 in the Journal of Clinical Medicine, but it only involved 200 women. In March 2023, a new publication nevertheless demonstrated its economic relevance, assuming a price of 750 euros. Its use in case of suspicion of endometriosis makes it possible to accelerate the diagnosis and therefore to reduce the cost. But other teams are already developing alternative devices. The Parisian start-up EndoDiag has designed a blood test in collaboration with reference hospitals in 12 countries (the Mayo Clinic in the United States, the Bern hospital in Switzerland, the CHU de Liège in Belgium, etc.). “We will begin clinical validation in the summer, then it will take a year of industrial development. The test should be available for sale in the summer of 2024”, explains CEO Cécile Real.
The French government seems to have taken the measure of what is at stake. Last year, he unveiled a “national strategy against endometriosis”, the second in the world after Australia. With the creation of “one of the largest epidemiological databases in the world” on this disease. “By the end of the year, each region must also set up a sector dedicated to endometriosis,” says the office of Minister of Health François Braun to L’Express. Finally, budgets will be released for research. Good news for all women, because the management of other gynecological pathologies (fibroids, infertility, etc.) should, in turn, benefit from advances in endometriosis.