Endometriosis is a common disease affecting approximately 190 million women of childbearing age, characterized by ectopic growth of tissue similar to the endometrium outside the uterine cavity, leading to severe chronic pain, infertility, and menstrual flow abnormalities. This disease has attracted much attention due to its significant impact on quality of life, but compared to other diseases with similar effects, research investment is seriously insufficient. This lack of investment has led to significant challenges in both basic research and the development of new treatment methods for diseases, particularly in understanding their complex pathological mechanisms and exploring innovative therapies. (Nature, “How understudied endometriosis causes pain for hundreds of millions of women “)
The pathogenic mechanism and biological basis of endometriosis
The pathogenesis of endometriosis is extremely complex, involving the interaction between pain neurons and immune cells. Research has shown that macrophages play a crucial role in the disease process, and the activation of pain-sensing nerves is not only responsible for pain perception, but may also exacerbate the condition by promoting the growth of lesion tissue. In other words, the interaction between pain neurons and immune cells may not only be the cause of pain, but also an important factor in promoting the development of diseased tissues. Therefore, a treatment plan that can both block pain signals and inhibit lesion expansion is expected to significantly alter the natural progression of the disease and improve patients’ quality of life.
In a study published in Science Translational Medicine, researchers revealed a key molecular pathway associated with endometriosis, which not only triggers pain perception but also plays an important role in disease progression. Specifically, researchers have found that a protein called calcitonin gene-related peptide (CGRP) plays an important role in the interaction between pain neurons and macrophages. The role of CGRP is not limited to the transmission of pain, but also promotes inflammation and expansion of lesions by regulating immune cells. This discovery provides a new perspective for the treatment of endometriosis.
In a mouse model, researchers significantly reduced the pain response of experimental mice and also reduced the size of lesions by using inhibitors of CGRP signaling. Research data shows that mice treated with CGRP inhibitors experienced a reduction in lesion volume of approximately 30% -50%. These results indicate that CGRP plays a crucial role in pain perception and lesion growth in endometriosis, suggesting that the CGRP signaling pathway may become a new target for treating this disease. In addition, the research team also observed that CGRP inhibitors can effectively reduce pain-related behaviors, further demonstrating the close relationship between CGRP and pain perception.
Our Related Proteins
| Cat. No. | Product Name | Source | Species | Tag |
| S100A11-2482H | Recombinant Human S100A11, GST-tagged | E.coli | Human | GST |
| S100A12-2483H | Recombinant Human S100A12, GST-tagged | E.coli | Human | GST |
| S100A11-3102H | Recombinant Human S100A11, None tagged | E.coli | Human | Non |
| CALCA-10658H | Recombinant Human CALCA, GST-tagged | E.coli | Human | GST |
| CALCA-3496H | Recombinant Human CALCA protein, His-tagged | E.coli | Human | His |
| CALCA-317H | Active Recombinant Human Calcitonin-related polypeptide alpha | Human | Human | Non |
| S100A12-3096H | Active Recombinant Human S100A12 protein(Met1-Glu92) | E.coli | Human | Non |
Limitations and challenges of existing treatment methods
At present, the treatment options for endometriosis are extremely limited. Commonly used hormone drugs can alleviate symptoms in some patients, but they are not suitable for all patients, especially those with fertility needs. In addition, although nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in pain management in the short term, long-term use can have adverse effects on liver and kidney function. Although surgery can temporarily remove ectopic lesions, the recurrence rate is relatively high, with data showing that about 50% -70% of patients experience recurrence within five years after surgery. Therefore, finding a new treatment method with fewer side effects and no negative impact on fertility is crucial for the long-term health management of patients.
Although hormone therapy is effective in some patients, its side effects, including weight gain, emotional fluctuations, and osteoporosis, result in up to 40% of patients being intolerant or unresponsive to it. The drawbacks of hormone therapy severely limit its long-term application, especially in young, family planning patients. In addition, long-term use of hormone drugs may also have adverse effects on the endocrine system, increasing the risk of developing other metabolic diseases. Therefore, developing new, non-hormonal treatment methods is currently one of the most urgent needs in this field.
Research progress and application prospects of CGRP inhibitors
In this study, the research team explored the role of CGRP in endometriosis. They used four CGRP inhibitors approved by the US Food and Drug Administration (FDA) for other diseases and applied these drugs to a mouse model with similar characteristics of endometriosis. The experimental results showed that two of the drugs significantly reduced the lesion size, reducing the lesion volume by 30% -50%. All four drugs were effective in reducing pain perception. These results indicate that CGRP is not only a mediator of pain, but it may also directly participate in the growth and maintenance of lesion tissue.
The potential applications of CGRP inhibitors go far beyond reducing pain. In animal models, the inhibitor showed inhibitory effects on inflammatory responses and reduced lesion expansion, further demonstrating the crucial role of CGRP in lesion growth. Suppose these findings can be validated in human clinical trials. In that case, CGRP inhibitors have the potential to become a non-hormonal treatment option, filling the current gap in the treatment of endometriosis. Since these drugs have already been applied in the market and are considered relatively safe, the research team is optimistic about their rapid advancement to the clinical stage. However, it should be noted that the safety of these drugs during pregnancy is not yet clear, especially for female patients planning to conceive, and further research is needed to ensure the safety of the medication.
Future research needs to explore the potential for combination therapy of CGRP inhibitors with other drugs. Considering the multifactorial pathogenesis of endometriosis, combination therapy may demonstrate better efficacy in controlling symptoms and reducing recurrence. Especially in the regulation of inflammation and immune response, the combination of other targeted immune drugs may further enhance the therapeutic effect.
The constraints of insufficient research investment on research
The research on endometriosis has always been plagued by insufficient funding. Compared to other diseases with similar universality and economic impact, research funding for endometriosis is at least two to three orders of magnitude less. The insufficient investment in scientific research greatly hinders the in-depth understanding of the pathological mechanisms of diseases and the development of new treatment methods. Michael Rogers, a cancer researcher at Boston Children’s Hospital, began to focus on the study of endometriosis after long-term persuasion from his church friends. Nine years ago, he began to establish an animal model for studying the disease, laying the foundation for subsequent research on CGRP inhibitors.
The insufficient funding for research has also limited the progress of clinical trials. Due to the lack of sufficient support, many potential new drugs and treatment strategies are difficult to enter the clinical trial stage, resulting in limited treatment options for patients. In addition, funding shortages have also affected the size and sustainability of research teams, and many excellent researchers have had to turn to other research fields due to a lack of stable funding support, further weakening the research power on endometriosis.
Erin Greaves, an endometriosis expert at the University of Warwick in the UK, stated that there is an urgent need for non-hormonal alternative therapies for the treatment of endometriosis. Although hormone therapy is effective in relieving symptoms, its side effects and negative impact on fertility have forced many patients to give up treatment. Therefore, CGRP inhibitors are expected to fill this gap and provide patients with a safer and more targeted treatment option.
Challenges from Basic Research to Clinical Application
Although researchers’ findings provide new hope for the treatment of endometriosis, the process from basic research to clinical application remains challenging. Firstly, the success of animal experiments cannot always be fully replicated in clinical trials, which involve species differences and complex human physiological characteristics. Secondly, considering the high heterogeneity of endometriosis, future clinical trials need to include patients of different ages, severity of the condition, and fertility needs to ensure the broad applicability and safety of treatment methods.
In addition, the diversity of endometriosis also means that a single treatment may be difficult to fully control the condition. Future research needs to further clarify the characteristics of different patients in order to develop personalized treatment plans. For example, for patients with severe conditions and infertility, a combination of surgery, medication, and assisted reproductive technologies may be necessary. Meanwhile, for patients with mild symptoms, non-hormonal medications and lifestyle adjustments may be sufficient to control the condition. Therefore, the concept of precision medicine is particularly important in the treatment of endometriosis.
In addition to drug therapy, strategies for comprehensive management of endometriosis are equally important. The combination of pain management, psychological support, and lifestyle adjustments can help patients better cope with the quality of life challenges brought by this chronic disease. The emergence of new drugs, if effective in reducing pain and inhibiting the growth of lesions, will greatly improve the quality of life of patients and enable them to regain control over their lives. The maintenance of mental health should also be included in comprehensive management. Chronic pain is often accompanied by anxiety and depression, and providing psychological counseling and support can help patients achieve comprehensive recovery.
Endometriosis, as a severely underestimated and far-reaching disease, affects the health and quality of life of hundreds of millions of women worldwide, and its research and treatment urgently require more attention and investment. The research on CGRP inhibitors provides a new direction for future treatments, by blocking the interaction between nerves and immune cells, both reducing pain and inhibiting lesion growth. If the safety and effectiveness of this dual-effect treatment strategy can be validated in clinical practice, it will bring new hope to many patients.
Related Products and Services
Protein Expression and Purification Services
Reference
Fattori, V., Zaninelli, T. H., Rasquel-Oliveira, F. S., Heintz, O. K., Jain, A., Sun, L., Seshan, M. L., Peterse, D., Lindholm, A. E., Anchan, R. M., Jr., A. V., & Rogers, M. S. (2024). Nociceptor-to-macrophage communication through CGRP/RAMP1 signaling drives endometriosis-associated pain and lesion growth in mice. Science Translational Medicine. https://doi.org/adk8230