According to the World Health Organization (WHO), endometriosis affects around 10% of people who menstruate, some 190 million people globally.
Symptoms, including severe pain during menstruation, heavy menstrual bleeding, back and pelvic pain, pain during intercourse, and, in some people, problems with fertility, occur when tissue similar to the endometrium, or uterine lining, grows outside the uterus.
Inflammation leads to the formation of lesions and scar tissue, so the condition tends to worsen over time.
Currently, endometriosis is treated with pain relief medication, such as non-steroidal anti-inflammatory drugs (NSAIDs), hormonal treatments that stop the ovaries from producing estrogen, and surgery.
Although these treatments can alleviate the symptoms, the condition is currently regarded as incurable.
Now, a Japanese study has found that a monthly injection of an engineered antibody that targets interleukin-8 (IL-8), an inflammatory cytokine, can reduce lesions, scar tissue, and organ adhesions in monkeys with endometriosis.
The research, published in Science Translational Medicine, suggests that this might lead to the first disease-modifying therapy for people with endometriosis.
Why use a monkey model?
The researchers used cynomolgus macaques, which are physiologically, biologically, and genetically close to humans in their study.
Female macaques menstruate, just like human ones, with an average menstrual cycle of around 30 days. They also develop endometriosis, with similar pathology to that which occurs in people.
Dr. Steven Vasilev, a board-certified integrative gynecologic oncologist and medical director of Integrative Gynecologic Oncology at Providence Saint John’s Health Center, professor at Saint John’s Cancer Institute in Santa Monica, CA, not involved in this study, explained for Medical News Today:
“Endometriosis in monkeys closely simulates [the] behavior of human endometriosis, making this an excellent model.”
What happened in the study
In this study, the researchers used monkeys with spontaneous endometriosis and others with endometriosis induced by transplanting endometrial tissue into the peritoneum.
The researchers developed an antibody — AMY109 — that binds to IL-8. They further engineered it so that it could target IL-8 multiple times, meaning the antibody had to be administered only once a month.
They injected AMY109 into one group of monkeys with endometriosis every 4 weeks for 6 months. A control group was given similar injections that did not contain the engineered antibody.
Dr. Vasilev told MNT that there was supporting evidence that this approach could work.
“An immunologic basis for the genesis and progression of endometriosis is already theorized and IL-8 is one of the known key proinflammatory cytokines in this process, and fibrosis in general,” he noted.
Inflammation and lesions reduced
The AMY109 injections had no adverse effects on the menstrual cycles of the monkeys, and they experienced no other side effects. But there was an improvement in their endometriosis.
The monthly subcutaneous injection of AMY109 reduced the volume of lesions and also diminished both fibrosis and adhesions.
“The authors developed a long-acting recycling antibody against IL-8 called AMY109 which objectively reduced inflammation and fibrosis associated with disease progression,” said Dr. Vasilev.
Unlike current hormone treatments, this anti–IL-8 antibody reduced fibrosis and adhesions in monkeys without affecting hormone secretion and menstruation.
However, the researchers were unable to confirm whether AMY109 also reduced the pain that the condition causes, or whether it improved fertility.
Dr. G. Thomas Ruiz, OB/GYN lead at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, not involved in this study, expressed some caution about the findings, but also a measure of hope: “It’s too soon to extrapolate to humans. But given the commonalities between primates and people, the data indicates it may be time to start human trials.”
And he stressed that it is very early days still: “We first need to establish safety and dosing for humans. Once that is completed, small trials will commence on volunteers.”
“Once stage 2 trials show safety and benefit, they can proceed to larger phase 3 trials to again analyze data across a large population,” he added. “Finally, the data will be reviewed by the FDA [Food and Drug Administration] for it to assess safety and efficacy.”
Possible future treatment
There is currently no cure for endometriosis, so treatments are targeted at managing symptoms, as Dr. Vasilev explained.
“There is a pressing need for disease-modifying drugs or biological agents to treat endometriosis,” he admitted. “Current pharmacological treatments, and newest clinical developments, are largely based on hormonal manipulation.”
“These are fraught with side effects and are limited to possibly providing pain relief but cannot cure the disease,” noted. Dr. Vasilev.
Surgery to remove lesions and adhesions is an option for those with severe endometriosis. It usually results in relief of pain, but at least one-third of those with the condition will need further surgery for continued problems.
This experimental antibody injection, might, according to Dr. Vasilev, help reduce the recurrence of endometriosis after surgery:
“Surgical excision is currently a cornerstone in [the] therapy of endometriosis. Surgery itself, in addition to the natural course of endometriosis, can produce fibrosis as part of the healing process. Reducing post-surgical fibrosis by modulating IL-8 may be an additional benefit in the multi-disciplinary medical and surgical management of endometriosis.”
So, if similar beneficial effects are seen in people, this finding could lead to the first disease-modifying treatment for endometriosis.
Although there is a long way to go before the antibody might be licensed for human use, this discovery should give hope to people with endometriosis.