Treating Fibroids at the Molecular Level
By Alicia Armeli

cells

By age 50, as many as 7 out of 10 white women and 9 out of 10 black women will develop uterine fibroids—a type of noncancerous growth responsible for painful bleeding, anemia, and infertility.1

Despite the commonness of this disease, its cause has eluded the scientific community—until now. Researchers are finding that molecular changes within a single uterine cell—specifically the extracellular matrix or ECM—may be the key to finding a cure for uterine fibroids.

No matter its location within the human body, ECM surrounds every cell. Although unique to each type of cell and tissue, ECM is essentially a fluid-like mixture made up of water, sugars, and proteins like collagen.

Because of its fluid-like flexibility, ECM provides organized cell structure and makes things such as communication within and between neighboring cells possible. Myometrial cells found in the uterine wall respond accordingly to such signals.

“Normal cells can be stretched or compressed by the ECM,” says Dr. Phyllis C. Leppert, MD, PhD, Emerita Professor of Obstetrics and Gynecology at Duke University in Durham, NC and President of the Campion Fund—a non-profit organization dedicated to raising money for public education and research in the field of reproductive sciences. “We know myometrial cells produce collagen that’s released into the space around the cells. If the ECM is stiff and isn’t flexible, it can put pressure on a cell, changing its shape and signaling it to produce even more collagen—as seen with uterine fibroids.”

This misfiring of signals is what Dr. Leppert and her colleagues addressed in a recent paper published in Obstetrics and Gynecology International.2 They found that these cells not only respond by producing more collagen but by producing collagen that is abnormal in comparison to healthy tissue. What’s more, these cells don’t go through cell death like normal cells would. Instead, they continue to replicate. Together, all of these factors could contribute to the perfect storm—an ideal environment for fibroid cells to perpetually grow.

“At this time, we don’t know exactly what triggers this cycle,” Dr. Leppert explains. “Uterine cells are much more sensitive to cell disruption. It could be injury to a cell, infection, or chronic inflammation. It’s also possible that there isn’t just one trigger but many causes working alone or together.”

Despite this uncertainty, Dr. Leppert is using what the scientific community already does know about fibroids. Targeting the abnormal collagen found in fibroids may lead to a new minimally invasive treatment option.

To test this theory, Dr. Leppert and a team of scientists at Duke University Medical Center used collagenase—an enzyme made by Clostridium histolyticum bacteria that is able to break down the abnormal collagen found in uterine fibroids.

The team of researchers used samples of fibroid tissue cut from uterine fibroids that were taken after the hysterectomies of seven consented patients. They then injected the tissue samples with highly purified collagenase, a diluting agent, or a placebo. Over the course of 4 days, the samples were incubated, monitored at varying checkpoints, and compared to untreated fibroid tissue samples.

Results were published earlier this year in the American Journal of Obstetrics and Gynecology.3 Before treatment, 37 to 77 percent fibrosis—caused by abnormal collagen—was seen in fibroid tissue samples. After treating fibroids with collagenase, fibrosis was reduced to levels that ranged between 2.4 and 5.3 percent—with complete breakdown of collagen.

Leppert and colleagues also noticed that fibroids became softer and lost their stiffness after treatment—especially when left to incubate longer. “The collagenase is very specific to breaking down collagen found in fibroid ECM,” Dr. Leppert discusses. “When this happens, the pressure on the fibroid cells decreases to that of normal uterine cells. We hope this will change cell signaling and cause fibroids to shrink, relieving bulk symptoms and easing pain and bleeding.”

To further understand its safety and tolerability in humans, collagenase is in the process of undergoing its first stages of clinical trials. By doing so, the scientific community hopes to understand who would benefit most from this treatment.

“Clinical trials will help find the best dosage, understand which fibroids it will work best on, and learn how to do the injection with precision,” Dr. Leppert continues. “It will also determine if single or multiple injections will be needed.  We also hope in the future to use it with additional drugs and will be planning studies to see with which drugs it will work best.”

By homing in on the cause of uterine fibroid growth, a cure may be that much more in reach. “Many of the treatments out there today are surgically oriented,” Dr. Leppert tells Ask4UFE. “To make better treatments available, we need to proactively work on the molecular aspect of the disease.”

ABOUT THE AUTHOR   Alicia Armeli is a Health Freelance Writer, Registered Dietitian Nutritionist, and Certified Holistic Life Coach. She has master’s degrees in English Education and Nutrition. Through her writing, she empowers readers to live optimally by building awareness surrounding issues that impact health and wellbeing. In addition to writing, she enjoys singing, traveling abroad and volunteering in her community.

ABOUT THE DOCTOR  Phyllis C. Leppert, MD, PhD, is an Emerita Professor of Obstetrics and Gynecology at Duke University in Durham, North Carolina. By focusing her research on molecular biology and the development of medical treatments for uterine fibroids, Dr. Leppert is dedicated to finding a treatment that targets the cause of fibroids. In addition to her research, Dr. Leppert also serves as president of the Campion Fund, a non-profit organization that raises money in support of public education and research in the field of reproductive sciences.

References

  1. US Department of Health and Human Services, National Institutes of Health. (2013). How many people are affected by or at risk of uterine fibroids? Retrieved June 22, 2016 from https://www.nichd.nih.gov/health/topics/uterine/conditioninfo/Pages/people-affected.aspx
  2. Leppert, P. C., Jayes, F. L., & Segars, J. H. (2014). The extracellular matrix contributes to mechnotransduction in uterine fibroids. Obstetrics and Gynecology International, Volume 2014 (2014), Article ID 783289, 12 pages. doi:  10.1155/2014/783289
  3. Jayes, F. L., Liu, B., Moutos, F. T., Kuchibhatla, M., Guilak, F., & Leppert, P. C. (2016). Loss of stiffness in collagen-rich uterine fibroids after digestion with purified collagenase Clostridium histolyticum. American Journal of Obstetrics and Gynecology. doi: 10.1016/j.ajog.2016.05.006