An experimental treatment for endometriosis, a painful gynecological condition that affects some 190 million people worldwide, may one day offer new hope for easing symptoms.
Monthly antibody injections reverse telltale signs of endometriosis in monkeys, researchers report on February 22 to Science Translational Medicine. The antibody targets IL-8, a molecule that stirs up inflammation inside the scattered, sometimes bleeding lesions that mark the disease. After neutralizing IL-8, these characteristic lesions shrink, the team found.
The new treatment is “quite powerful”, says Philippa Saunders, a reproduction scientist at the University of Edinburgh who was not involved in the work. The study authors did not report a cure, she points out, but their antibody appears to be having an impact. “I think it’s really very promising,” she said.
Many scientists believe that endometriosis occurs when pieces of the uterine lining – the endometrium – break off during menstruation. Instead of exiting through the vagina, they travel the other way: through the fallopian tubes. These bits of tissue then travel through the body, sprouting lesions where they land. They’ll settle on the ovaries, fallopian tubes, bladder and other places outside the uterus and take on a life of their own, Saunders says.
Lesions can grow nerve cells, form hard tissue bumps, and even bleed during menstrual cycles. They can also trigger chronic episodes of pelvic pain. If you have endometriosis, you may experience “pain when urinating, pain when defecating, pain when having sex, pain when moving around,” says Saunders. People with the condition may also struggle with infertility and depression, she adds. “It’s really mean.”
Once diagnosed, patients face a dearth of treatment options – there is no cure, only therapies to relieve symptoms. Surgery to remove lesions can help, but symptoms often return.
The disease affects at least 10% of transgender girls, women and men of childbearing age, Saunders says. And people usually suffer for years – about eight on average – before a diagnosis. “Doctors consider menstrual pelvic pain to be a very common thing,” says Ayako Nishimoto-Kakiuchi, pharmacologist at Chugai Pharmaceutical Co. Ltd. in Tokyo. Endometriosis “is clinically underestimated,” she says. “I strongly believe that this disease has been understudied.”
Hormone drugs that stop ovulation and menstruation may also offer relief, says Serdar Bulun, a reproductive endocrinologist at Northwestern University Feinberg School of Medicine in Chicago, not involved in the new study. But these drugs have side effects and are not ideal for people trying to get pregnant. “I see these patients day in and day out,” he says. “I see how much they are hurting and I feel like we’re not doing enough.”
Nishimoto-Kakiuchi’s team designed an antibody that latches on to the inflammatory factor IL-8, a protein that scientists have previously identified as one of the potential culprits of the disease. The antibody acts like a garbage collector, says Nishimoto-Kakiuchi. It grabs the IL-8, delivers it to the cell’s waste disposal machinery, then heads for more IL-8.
The team tested the antibody in cynomolgus monkeys that had been surgically engineered to have the disease. (Endometriosis rarely appears spontaneously in these monkeys, the scientists found after examining more than 600 females.) The team treated 11 monkeys with the antibody injection once a month for six months. In these animals, the lesions have shrunk and the adhesive tissue that sticks them to the body has also thinned. Prior to this study, Nishimoto-Kakiuchi says, the team did not believe such signs of endometriosis were reversible.
His company has now launched a phase I clinical trial to test the safety of the therapy in humans. Treatment is one of many endometriosis therapies scientists are testing (SN: 07/19/19) . Other trials will test new hormonal drugs, robot-assisted surgery and behavioral interventions.
Doctors need new options to help people with the disease, Saunders says. “There is a huge unmet clinical need.”