Unravelling the potential of galectin inhibitors and nanotechnology as therapeutic options for endometriosis treatment

Project lead: María Martínez-Esparza, University of Murcia

Participating universities: University of Murcia, Nantes Université, University of Santiago de Compostela

General overview

Galectin inhibitors 1 and 3, and their role on macrophages, represent promising therapeutic options for the treatment of endometriosis. The aim of this project is to evaluate their potential therapeutic value. The project objectives are as follows:

1. Design and synthesise highly specific inhibitors for galectin-1 and 3.

2. Encapsulate the galectin inhibitors in biomimetic nanoparticles to promote their delivery.

3. Screen and compare galectin inhibitors and encapsulated formulations in a macrophage cell line in vitro model.

4. Evaluate the bioactivity of commercially available galectin-1 and 3 inhibitors and formulations in peritoneal macrophages from endometriosis patients.

Purpose and Significance

Endometriosis is a highly prevalent chronic inflammatory disease of the reproductive system in women of childbearing age. It mainly manifests as abdominal pain and infertility. Currently, endometriosis is usually treated through medical therapy and surgery. However, due to the high recurrence rate and many complications, it has a significant impact on patients’ quality of life. For this reason, it is important to develop effective approaches to treat this disease. 

Implementation Method and Timeline

Design and synthesis of galectin inhibitors. (Nantes Université) 

  • Synthesis and modifications of the inhibitors. 
  • In vitro testing of the inhibitors. 

Design and characterisation of biomimetic nanocarriers for encapsulation of galectin 1/3 inhibitors (University of Santiago de Compostela)

  • Encapsulation of commercially available inhibitors in biomimetic nanocarriers. 
  • Encapsulation of newly synthesised inhibitors in biomimetic nanocarriers. 

 Evaluation of in vitro activity of galectin- 1/3 inhibitors in human macrophages(University of Murcia)

  • Determination of galectin-1/3 levels in macrophage cell cultures, and clinical samples from healthy controls and endometriosis patients. 
  • Evaluation of the effect of free or encapsulated galectin-1/3 commercially available inhibitors (TD139), in an in vitro cell line model of human macrophages. 
  • Analyse the effect of the most effective doses and nano formulations of TD139 galectin-1/3 inhibitor in human peritoneal macrophages of endometriosis patients.
  • Assay new synthesised high specific galectin-1/3 inhibitors in an in vitro cell line model of human macrophages. 

Expected Outcomes

Endometriosis is a systemic disease, often painful and chronic, that affects around 10% of reproductive-age women. It can have a negative impact on a patient’s physical and emotional well-being, quality of life, and productivity. Furthermore, partly due to the societal normalisation of women’s pain and stigma around menstrual issues, there is also a lack of disease awareness among patients, healthcare providers, and the public. As a result, endometriosis is under-researched, greatly limiting our understanding of the disease and slowing much-needed innovation in diagnostic and treatment options. Therefore, this project has the potential to have a tremendous societal impact that will open new areas of research and a new line of actuation.

The research will lead to high-impact publications due to the novelty of the expected results. Also, the multi-disciplinarity of the approaches will provide high-quality evidence and new advancements.

In addition, the industrial interest in commercialising products in this area is also a promising feature. By using bottom-up techniques from chemical biology, nanochemistry and self-assembly procedures, the synthesis of galectin-biomimetic nanoformulation products that are relatively easy to manufacture, biocompatible and safe, will be developed. The success of this project could be highly beneficial for the treatment of other diseases such as cancer, infectious diseases or auto-immune diseases. The group intends to patent any result that will be suitable for that.