Tapeworm Drug Shows Promise in Shrinking Endometriosis Lesions in Mice
A decades-old anti-parasitic medication, niclosamide, is being investigated in a novel, targeted form for its potential to treat endometriosis, a condition affecting millions of women.
Scientists are exploring a repurposed tapeworm drug, niclosamide, as a potential new treatment for endometriosis, a condition characterized by debilitating pain and infertility that affects approximately 1.5 million women in the UK.
Niclosamide has been in use for decades to eliminate gut parasites by blocking their glucose supply. Now, researchers in the U.S. have developed a highly targeted version of the drug. In animal studies, this modified drug has demonstrated the ability to reduce lesions formed by endometrial tissue that has grown outside the uterus. This displaced tissue can implant on organs such as the ovaries, bowel, bladder, and in rarer cases, even the spine, lungs, or brain. Each month, during menstruation, this tissue swells and bleeds, leading to inflammation, pain, and scar tissue formation, a process known as adhesion.
Endometriosis is also a significant factor in female infertility. Due to a lack of awareness, the average time for a diagnosis can exceed nine years, according to Endometriosis UK. Current treatments vary from over-the-counter pain relievers and hormonal contraceptives to surgical removal of excess tissue or, in severe cases, hysterectomy.
A New Therapeutic Avenue
Niclosamide's potential as a treatment for endometriosis stems from its documented ability to inhibit key signaling pathways that regulate cell growth across various diseases. Its application is also being investigated for conditions including kidney disease, COVID-19, diabetes, and several types of cancer. Research suggests it can trigger self-destruction in mitochondria, the energy-producing components of cells, including cancerous ones.
A significant challenge with oral niclosamide is its poor solubility in water, which limits its absorption into the bloodstream and thus its ability to reach endometriosis lesions. To overcome this, researchers at Washington State University engineered a water-soluble, tree-shaped molecule called a dendrimer. This structure was loaded with niclosamide and then injected.
The dendrimer's design allows it to carry small drug molecules. Furthermore, it contains folic acid, which binds to FR-beta, a protein found on the surface of immune cells that accumulate in lesions and inflamed areas. Endometrial lesions have been observed to have a high concentration of FR-beta cells, believed to contribute to the disease's progression and chronic pain.
Promising Results in Animal Models
Researchers tested the drug-loaded dendrimers on mice genetically engineered to have endometriosis. Injections were administered directly into the abdomen, near the lesion sites. After two weeks, a significant reduction in detectable lesions was observed. Four out of eight mice receiving a low dose and five out of eight on a high dose showed no remaining lesions, indicating a potential cure. The mice also exhibited reduced pain sensitivity, with these benefits persisting for at least two weeks.
Anjali Sharma, an associate professor of pharmaceutical sciences at the University of Michigan and a member of the research team, highlighted the difficulties in developing safe and effective long-term treatments for endometriosis, stating, "One of the major challenges has been developing treatments that are both effective and safe for long-term use. Our goal is to address the underlying disease pathology and ultimately improve the quality of life for millions of women."
The researchers envision that this injectable form of niclosamide could eventually be administered as a bi-weekly injection. Once in the bloodstream, it would circulate, targeting FR-beta immune cells within endometrial lesions.
Andrew Horne, a professor of gynaecology and reproductive sciences at the University of Edinburgh, described targeting the immune system as a promising approach, noting that repurposing an existing drug could expedite development. However, he cautioned that the study represents a very early stage.
Horne pointed out that a primary limitation is the study's reliance on mice, which do not experience menstruation or naturally develop endometriosis. Consequently, there is no guarantee of similar efficacy in humans. He also noted the study's small scale and short duration, focusing on lesion reduction and pain behavior rather than long-term outcomes. Questions remain about the treatment's long-term safety, required dosage frequency, and overall effectiveness in human patients.