title: c-Jun NH2-terminal kinase inhibitor bentamapimod reduces induced endometriosis in baboons: an assessor-blind placebo-controlled randomized study.
abstract: OBJECTIVE
  To test the hypothesis that the c-Jun NH2-terminal kinase (JNK) inhibitor (JNKI) bentamapimod (AS602801/PGL5001) can reduce induced endometriosis in baboons.
  
  
  METHODS
  Prospective randomized placebo-controlled study.
  
  
  METHODS
  Nonhuman primate research center.
  
  
  METHODS
  Twenty baboons each underwent four laparoscopies. Initial screening laparoscopy (L1) was followed after one rest cycle by an endometriosis-induction laparoscopy (L2). Fifty days after L2, the baboons were randomized just before staging laparoscopy (L3). Treatment lasted for 60 days, followed by a post-treatment staging laparoscopy (L4).
  
  
  METHODS
  Randomization before a 60-day treatment in four groups: daily placebo (n = 5), daily oral administration of 20 mg/kg JNKI (n = 5), concomitant daily oral administration of 20 mg/kg JNKI and 10 mg medroxyprogesterone acetate (MPA; n = 5), or subcutaneous administration of 3 mg cetrorelix every 3 days (n = 5).
  
  
  METHODS
  Type, surface area and volume of endometriotic lesions, and revised American Society for Reproductive Medicine score and stage were recorded during L3 and L4. Menstrual cycle length and serum hormonal concentration were recorded before and after treatment.
  
  
  RESULTS
  Compared with placebo, treatment with JNKI, JNKI + PMA, or cetrorelix resulted in lower total surface area and volume of endometriotic lesions. Remodeling of red active lesions into white lesions was observed more frequently in baboons treated with JNKI + MPA than in baboons treated with JNKI only. Menstrual cycle length and serum hormonal concentration were similar between placebo and JNKI groups.
  
  
  CONCLUSIONS
  JNKI alone was as effective as JNKI + MPA or cetrorelix in reducing induced endometriosis in baboons, but without severe side effects or effect on cycle length or serum reproductive hormones.
authors.affiliation: Department of Obstetrics and Gynecology, Assiut University Hospitals, Assiut, Egypt; Institute of Primate Research, Karen, Nairobi, Kenya.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Hussein
authors.affiliation: Institute of Primate Research, Karen, Nairobi, Kenya.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Chai
authors.affiliation: Institute of Primate Research, Karen, Nairobi, Kenya.
authors.forename: Cleophas M
authors.initials: CM
authors.lastname: Kyama
authors.affiliation: Institute of Primate Research, Karen, Nairobi, Kenya.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Mwenda
authors.affiliation: TocopheRx, Burlington, Massachusetts.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Palmer
authors.affiliation: Preglem, Reproductive Medicine, Geneva, Switzerland.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gotteland
authors.affiliation: Institute of Primate Research, Karen, Nairobi, Kenya; Leuven University Fertility Center, Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, Leuven, Belgium. Electronic address: thomas.dhooghe@uz.kuleuven.ac.be.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: D'Hooghe
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004715:Endometriosis / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D004717:Endometrium / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D006728:Hormones / Q000097:blood; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010535:Laparoscopy; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D008597:Menstrual Cycle / Q000187:drug effects; D048530:Papio anubis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D052160:Benzothiazoles; D006728:Hormones; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D007987:Gonadotropin-Releasing Hormone; D017258:Medroxyprogesterone Acetate; D048031:JNK Mitogen-Activated Protein Kinases; C062876:cetrorelix; C000609147:bentamapimod
keywords: JNK; baboons; biomarkers; endometriosis; endometriotic lesions