Our project has a long and exciting history that highlights the collaborative nature of science and our team's persistence and enthusiasm for our work. The conception of this project began with the research of Dr. Phyllis Leppert at the National Institutes of Health (NIH) in 2004.
Since the project's inception in 2004, we have been studying uterine fibroid biology and researching a potential novel investigational therapy. The development program has expanded to include collaborations with Duke, North Carolina Central University (NCCU), Johns Hopkins University (JHU) and North Carolina State University (NCSU). Funding support has been achieved through support and awards from NIH BIRWCH, Advance Biofactures Corporation, Duke CTSI Accelerator, and North Carolina Biotechnology Center.
Although not currently available to treat patients, we will continue studying the collagenase + Liquogel™ combination with the hope that in the future this novel, currently investigational, therapy will be available as an approved, commercial product.
2004
Uterine fibroid composition discovered
Project collaborators Dr. Phyllis Leppert (NIH)& Dr. James Segars (NIH) publish work showing uterine fibroids were composed of altered collagen.
2005
Dr. Taylor joins NCCU
Taylor joins NCCU as assistant professor in chemistry.
2006
Dr. Leppert joins Duke
Leppert joins Duke as professor of obstetrics and gynecology and professor of pathlogy.
2008
Dr. Taylor develops a novel drug delivery system
Under Dr. Donald McDonnell's (Duke) mentorship, Dr. Taylor develops a drug delivery system for breast cancer therapy.
2008
Dr. Jayes focuses on uterine fibroid research
Jayes joins the lab of Dr. Phyllis Leppert, the program director for Duke NIH BIRWCH (Building Interdisciplinary Research Careers in Women's Health), to research uterine fibroids.
2008
Dr. Jayes and Dr. Taylor meet
Taylor appointed a K12 NIH BIRWCH scholar and brings Leppert into her mentor team, where she and Jayes bond over their joint interest in uterine fibroid therapy.
2009
Jayes-Taylor collaboration begins
Collaboration involves Taylor expanding the scope of her drug delivery system, later called LiquoGel™, to treat uterine fibroids. Jayes joins BIRCWH as the program coordinator and researched how to target the collagen composition of uterine fibroids.
2010
European Connective Tissue Conference presentation
Leppert (Duke) and Segars (NIH) present uterine fibroid studies at the European Connective Tissue meeting discussing how collagenase Clostridium histolyticum (CCH) may be an effective treatment for uterine fibroids.
2011
Drug Delivery System research published
Taylor publishes "Temperature-Responsive Biocompatible Copolymers Incorporating Hyperbranched Polyglycerols for Adjustable Functionality" along with colleagues Jayes, House, and Ochieng in The Journal of Functional Biomaterials.
2012
Ex vivo collagenase studies
Duke's scientists publish work showing significant softening of human fibroid tissue by injecting a highly purified enzyme (Clostridium Histolyticum collagenase (CHC)) that can degrade the collagen in fibroids.
2015
Dr. James Segars joins Johns Hopkins University
Segars joins Johns Hopkins University as professor and director of reproductive science and women’s health research, in the department of gynecology and obstetrics.
2015
Combination therapy studies ex vivo
Taylor awarded the Delta Sigma Theta Distinguished Professor Endowed Chair, enabling the team to undertake ex vivo studies assessing combination collagenase LiquoGel™ efficacy for degrading uterine fibroids.
2016
Collagenase study published in the American Journal of Obstetrics and Gynecology
Jayes publishes the study “Loss of stiffness in collagen-rich uterine fibroids after digestion with purified collagenase Clostridium histolyticum” with colleagues Liu, Moutos, Kuchibhatla, Guilak, and Leppert.
2016
Phase 1 Interventional Clinical Trial
Clinical Trial NCT02889848 completed on “Safety and Tolerability of Collagenase Clostridium Histolyticum (EN3835) to Treat Uterine Leiomyoma (Fibroids).” See publications in 2021.
2018
American Institute of Chemical Engineers (AIChE) Conference Presentation
Jayes and Taylor present work titled “Developing an Injectable, Enzymatic Treatment for Uterine Fibroids: Using Rheology and Histology to Quantify Therapeutic Efficacy” at the AIChE meeting in Pittsburgh, PA.
2019
Study published on composition heterogeneity of uterine fibroids
Jayes publishes “Evidence of biomechanical and collagen heterogeneity in uterine fibroids” in PLOS One with colleagues Liu, Feng, Aviles-Espinoza, Leikin, and Leppert.
2019
Duke-NCCU CTSI Consortium Collaborative Translational Research Award
Duke CTSI Accelerator awards Jayes and Taylor a collaborative interinstitutional grant to scale the production of LiquoGel™, characterize the product batches and evaluate the entrapment and release of active collagenase as well as covalent linked model drugs.
2021
Translational Research Grant (TRG) from NC Biotech
Collaborative grant between Jayes and Taylor to expand on the uterine fibroid project. Jayes successfully develops standard operating procedures for preparing larger batches (20 g) of LiquoGel™. The prior batch maximum was 5g. The 20g batch has a purity over 98%, as confirmed by nuclear magnetic resonance spectroscopy.
2021
Collagenase LiquoGel™ study published in Acta Biomaterialia
Taylor and Jayes publish "Using rheology to quantify the effects of localized collagenase treatments on uterine fibroid digestion" with colleagues Corder, Gadi, Vachieri, Cullen, and Khan.
2021
Study published showing importance of Hippo pathway in uterine fibroid growth
Study published in Clinical Translational Medicine titled “Extracellular matrix and Hippo signaling as therapeutic targets of antifibrotic compounds for uterine fibroids” by Islam, Afrin, Singh, Jayes, Brennan, Borahay, Leppert, and Segars. First report that in vivo injection of collagenase into uterine fibroids reduced Hippo/YAP signaling and crucial genes and pathways involved in fibroid growth. These results indicate that targeting ECM stiffness and Hippo signaling might be an effective strategy for uterine fibroids.
2021
Phase 1 Clinical Trial Study published
Study published in the Journal of Reproductive Sciences titled "A Phase I Clinical Trial to Assess Safety and Tolerability of Injectable Collagenase in Women with Symptomatic Uterine Fibroids" by Singh, Sims, Trueheart, Simpson, Wang, Patzkowsky, Wegman, Soma, Dixon, Jayes, Voegltine, Yenokyan, Su, Leppert, and Segars.
Uterine fibroid size and patient pain scores were decreased following treatment of uterine fibroids with collagenase.
2024
Planned Activity: LiquoGel™ scaling
Scale up LiquoGel™ manufacturing for use in future clinical trial and ex vivo studies.
2024
Planned Activity: Phase 1B/2 Clinical Trial
2024
Planned Activity: Combination collagenase Liquogel™ studies
Optimization and expansion of ex vivo studies to assess the efficacy of collagenase and LiquoGel™ combination investigational therapy in uterine fibroids.
2024
Advance Development
Continue investigational drug development studies, clinical studies and raise funding to advance the investigational therapy to an approved commercial product.
Evaluation of treatment preference and access for women, families, and communities affected by uterine fibroids.