Endometriosis (EMS) is a chronic inflammatory disease of multifactorial etiology characterized by implantation and growth of endometrial glands and stroma outside the uterine cavity. EMS is a significant public health issue as it affects 15-20% of women in their reproductive age. Clinical symptoms may include
pelvic pain,
dysmenorrhea,
dyspareunia, pelvic/abdominal masses, and
infertility. Symptomatic treatments such as surgical resection and/or hormonal suppression of ovarian function and
analgesics are not as effective as desired. Consequently, there is an enormous unmet need to develop effective medical
therapy capable of preventing the occurrence and recurrence of EMS without undesirable side-effects. EMS-associated intra-abdominal
bleeding episodes, local
inflammation, adhesions, and i.p. immunologic dysfunction leads to pelvic nociception and
pelvic pain. Increasing evidence supports the involvement of allergic-type
inflammation in EMS. Invasion of mast cells, degranulation, and proliferation of interstitial component are observed in endometriotic lesions. Presence of activated and degranulating mast cells within the nerve structures can contribute to the development of
pain and
hyperalgesia by direct effects on primary nociceptive neurons. Therefore, treatments targeting endometrial mast cells may prove effective in preventing or alleviating EMS-associated symptoms. The
Janus kinase 3 (JAK3) is abundantly expressed in mast cells and is required for the full expression of high-affinity
IgE receptor-mediated mast cell inflammatory sequelae. JANEX-1/
WHI-P131 is a rationally designed novel JAK3 inhibitor with potent anti-inflammatory activity in several cellular and in vivo animal models of
inflammation, including mouse models of
peritonitis,
colitis,
cellulitis,
sunburn, and airway
inflammation with favorable toxicity and pharmacokinetic profile. We hypothesize that JAK3 inhibitors, especially
JANEX-1, may prove useful to prevent or alleviate the symptoms of EMS.