Light at the End of the Tunnel? Antibody Therapy for Endometriosis
After years of diagnosis, enduring years of suffering, and extensive years of research, a definitive causal therapy for the chronic condition of endometriosis remains elusive. Researchers across the globe are dedicatedly pursuing this paramount objective, sharing their current findings. One such instance involves a Japanese research team led by Nishimoto-Kakiuchi, actively developing an antibody therapy targeting endometriosis. The inaugural outcomes of their study have recently been unveiled in the esteemed journal “Science”[1].
Antibody therapy constitutes a form of immunotherapy. At its core, it leverages the immune system to combat specific illnesses. Antibodies are either directly administered or the immune response is triggered through medications. In cases marked by heightened inflammatory activity, the immune system can also be selectively modulated. This therapeutic approach is already harnessed in the treatment of cancer, autoimmune disorders, infections, and even migraines [2].
In recent years
… immunotherapy has also gained significant prominence in the realm of endometriosis research.
Initial basic research unveiled that endometriosis is intricately linked with escalated and irregular inflammatory processes. Elevated immune system cells were identified at the sites of endometriosis lesions, alongside heightened levels of specific immune defense messenger substances (such as TNF-alpha, IL-6, IL-8, etc.) [3].
Building upon these disease-related discoveries, the inaugural immunotherapy investigations were carried out worldwide [4, 5, 6, 7]. For instance, a research team at Mansoura University in Egypt examined an antibody targeting the IL-6 receptor. Following antibody administration, the endometriosis lesions in the tested mice exhibited a reduction in size compared to the control group [5].
In a recent notable development, a Japanese study focusing on antibodies against the IL-8 receptor has garnered attention [1]:
The team of scientists led by Nishimoto-Kakiuchi embarked on research involving primary species macaques, which naturally developed endometriosis.
During the analysis of abdominal fluid, they identified IL-8 concentration as the highest compared to other messenger substances. Furthermore, a correlation was established between IL-8 concentration levels and the severity of endometriosis (as per rASRM). This revealed that more severe endometriosis correlated with elevated IL-8 concentration, consequently leading to heightened inflammatory responses in the body.
Leveraging these findings, the AMY109 antibody was formulated and subjected to testing in macaques afflicted with endometriosis. Ultimately, four test subjects received monthly doses of the AMY109 antibody for a year. Over this period, abdominal ultrasonography was conducted every three months to assess the progression of endometriosis.
Among the results, two primates exhibited a noteworthy reduction in condition severity, transitioning from rASRM stages III & IV to stages II & III. This reduction was not only observed in the endometriosis lesions but also in the tissue adhesions. Another macaque displayed no alteration in the condition stage, mirroring the fourth test subject, where a progressive condition process was noted in the initial half of the study, followed by a consistent condition stage. Notably, apart from localized skin vaccination reactions, no side effects emerged. While the prospect of an extended testing period raises questions about whether the other two subjects would also demonstrate a decrease in endometriosis, the drug’s efficacy in humans remains uncertain. This uncertainty is compounded by the need to consider potential changes in pain levels, other symptoms, or fertility that could arise in human subjects.
Study Phases in Brief:
Phase 1:
In this stage, a small group of healthy female volunteers undergo testing, primarily to assess potential side effects.
Phase 2:
The focus shifts to a limited number of patients for dosage determination and evaluation of effects and side effects.
Phase 3:
A pivotal phase involving larger study populations, aiming to secure marketing approval – a process that may span several years.
Phase 4:
Following successful market approval, observation during clinical usage becomes paramount.
For the development
… and approval of novel therapeutic options, particularly medications, a series of distinct study phases (outlined in the Infobox) is indispensable. Consequently, the developmental journey can span several years to decades, aiming to ensure the utmost patient safety – although the success of the drug cannot be guaranteed.
Upon surmounting the pivotal hurdle of approval, fresh challenges may arise. Historically, antibody-based therapies have proven to be financially demanding and can impose a strain on healthcare systems. Moreover, the availability of these drugs might be constrained by production capacities and infrastructure limitations.
It is crucial to underscore that antibody therapy may not be universally suitable for all patients, whether due to common side effects or other existing health conditions. A new therapy avenue employing antibodies would not outright replace existing forms of treatment, such as hormonal or surgical therapies, but rather complement them. In conclusion, ongoing research into endometriosis therapy holds promise. When a definitive cure might not be on the immediate horizon, the path of research is already yielding vital insights into the nature of the disease.
We will eagerly monitor further research on antibody therapy and provide updates as new findings emerge.
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References
- Nishimoto-Kakiuchi A, Sato I, Nakano K, Ohmori H, Kayukawa Y, Tanimura H, Yamamoto S, Sakamoto Y, Nakamura G, Maeda A, Asanuma K, Kato A, Sankai T, Konno R, Yamada-Okabe H. A long-acting anti-IL-8 antibody improves inflammation and fibrosis in endometriosis. Sci Transl Med. 2023 Feb 22;15(684):eabq5858. doi: 10.1126/scitranslmed.abq5858. Epub 2023 Feb 22. PMID: 36812343. Seen on: https://pubmed.ncbi.nlm.nih.gov/36812343/
- https://www.journalonko.de/thema/lesen/immuntherapie Zuletzt geöffnet: 02.03.2023)
- Chopyak VV, Koval HD, Havrylyuk AM, Lishchuk-Yakymovych KA, Potomkina HA, Kurpisz MK. Immunopathogenesis of endometriosis – a novel look at an old problem. Cent Eur J Immunol. 2022;47(1):109-116. doi: 10.5114/ceji.2022.113830. Epub 2022 Mar 6. PMID: 35600152; PMCID: PMC9115599. Seen on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115599/
- Kaplan S, Kırıcı P, Türk A. The effects of adalimumab on the rat autotransplantation endometriosis model: A placebo-controlled randomized study. Adv Clin Exp Med. 2022 Apr;31(4):417-426. doi: 10.17219/acem/144369. PMID: 35040600
seen on: https://pubmed.ncbi.nlm.nih.gov/35040600/ - El-Zayadi AA, Mohamed SA, Arafa M, Mohammed SM, Zayed A, Abdelhafez MS, Badawy AM. Anti-IL-6 receptor monoclonal antibody as a new treatment of endometriosis. Immunol Res. 2020 Dec;68(6):389-397. doi: 10.1007/s12026-020-09153-5. Epub 2020 Sep 17. PMID: 32939649
Seen on: https://pubmed.ncbi.nlm.nih.gov/32939649/ - Koninckx PR, Craessaerts M, Timmerman D, Cornillie F, Kennedy S. Anti-TNF-alpha treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial. Hum Reprod. 2008 Sep;23(9):2017-23. doi: 10.1093/humrep/den177. Epub 2008 Jun 12. PMID: 18556683; PMCID: PMC2517154.
Seen on: https://pubmed.ncbi.nlm.nih.gov/18556683/ - Kolanska K, Alijotas-Reig J, Cohen J, Cheloufi M, Selleret L, d’Argent E, Kayem G, Valverde EE, Fain O, Bornes M, Darai E, Mekinian A. Endometriosis with infertility: A comprehensive review on the role of immune deregulation and immunomodulation therapy. Am J Reprod Immunol. 2021 Mar;85(3):e13384. doi: 10.1111/aji.13384. Epub 2020 Dec 19. PMID: 33278837.
Seen on: https://pubmed.ncbi.nlm.nih.gov/33278837/ - https://www.dimdi.de/dynamic/de/glossar/glossareintrag/Studienphasen/ Stand: 02.03.2023
- https://de.gsk.com/de-de/forschung-und-entwicklung/klinische-studien/phasen-der-klinischen-pruefung/ Stand: 02.03.23
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