A potential new treatment for endometriosis, a painful chronic condition affecting about 190 million women worldwide, is showing promise after researchers modified an existing drug to target cells involved in the disease.
Researchers at Washington State University modified niclosamide, a drug used to treat parasitic infections, and tested the new formulation in mice with endometriosis lesions. The results were encouraging, according to a study published in the scientific journal Advanced Healthcare Materials.
If the findings can be replicated in humans, they could open a new chapter in the treatment of endometriosis, said Kanako Hayashi, a professor of reproductive biology at Washington State University and the study’s lead author.
Why current treatments have limitations
Endometriosis typically develops between puberty and menopause. It occurs when cells similar to those lining the inside of the uterus grow outside the uterus, forming lesions.
Current treatments generally involve surgery to remove the lesions, hormone therapy or a combination of the two. However, these approaches can cause complications and are often ineffective over the long term.
The condition can cause severe abdominal and pelvic pain, which often worsens during menstruation, and is also associated with fertility problems.
Despite its effects, endometriosis remains underdiagnosed and undertreated. One reason is that definitive diagnosis has traditionally required surgery to identify lesions outside the uterus. Excessive menstrual pain is also often treated as normal, which can delay recognition of the condition.
Nearly half experience recurrence
The limitations of existing treatments make the search for alternatives particularly important.
Nearly half of women who undergo surgery to remove endometriosis lesions experience a recurrence within five years.
Hormonal treatments can also cause side effects including depression, hot flashes and osteoporosis, while they can often prevent women from becoming pregnant.
The problem with niclosamide
Hayashi discovered as early as 2016 that niclosamide’s anti-inflammatory properties prevented the growth of endometrial tissue that had been introduced into mice.
However, the drug has a major limitation: It is poorly absorbed by the body because of its low solubility in water.
As a result, high doses are needed for it to be effective. Such doses can cause nausea, loss of appetite and stomach cramps.
The U.S. Food and Drug Administration has therefore approved niclosamide for use for no more than seven consecutive days. That makes the drug impractical for treating a chronic condition that requires longer-term management.
Researchers modify the drug
Hayashi and her colleagues modified niclosamide so it could potentially be administered safely over longer periods.
They attached the drug to a tiny water-soluble delivery vehicle measuring less than eight nanometers in length.
The researchers also modified the drug to specifically target the cells responsible for the lesions by adding folic acid to its chemical structure.
The decision to use folic acid was based on an earlier study in which the researchers found that some of the macrophages — immune-system cells — involved in endometriosis have receptors for folic acid.
Promising results in mice
The researchers administered the modified niclosamide to mice that had developed endometriosis lesions.
The treated mice showed reduced sensitivity to pain and developed fewer and smaller lesions than mice in the control group.
The researchers also found that the drug remained inside the macrophages responsible for the lesions for at least two weeks.
That finding suggests the modified drug could eventually be administered by injection every few weeks, similar to some medications currently used to treat migraines and diabetes.
Patients seek new treatment options
Hayashi emphasized that the experiments in mice represent only a first step and that there is still a long road before the treatment could be tested in humans.
But the demand for new treatment options among endometriosis patients is already clear.
After the study was published, Hayashi said she received “tons” of emails from patients asking to participate in future clinical trials.
