c-Jun NH2-terminal kinase inhibitor bentamapimod reduces induced endometriosis in baboons: an assessor-blind placebo-controlled randomized study

Hussein M, Mostafa Hussein, Daniel C Chai, Daniel Chai, Cleophas M Kyama, Cleophas Kyama, Jason M Mwenda, Mwenda JM, Stephen S Palmer, Palmer SS, Stephen Palmer, Jean-Pierre Gotteland, Gotteland JP, Jean‐Pierre Gotteland, D'Hooghe TM, Thomas D’Hooghe, Thomas M D'Hooghe
Fertility and sterility · 2015 · vol. 105(3) , pp. 815–824.e5 · doi:10.1016/j.fertnstert.2015.11.022 · PMID:26654972 · W2181782164
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Bentamapimod, a c-Jun NH2-terminal kinase inhibitor, was found to reduce induced endometriosis in baboons in a blinded, placebo-controlled, randomized study.

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Abstract

ObjectiveTo test the hypothesis that the c-Jun NH2-terminal kinase (JNK) inhibitor (JNKI) bentamapimod (AS602801/PGL5001) can reduce induced endometriosis in baboons.DesignProspective randomized placebo-controlled study.SettingNonhuman primate research center.Animal(s)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).Intervention(s)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).Main outcome measure(s)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.Result(s)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.Conclusion(s)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.

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Condition tags

endometriosis

MeSH descriptors

Benzothiazoles Endometriosis Endometrium JNK Mitogen-Activated Protein Kinases Protein Kinase Inhibitors Pyrimidines Signal Transduction Animals Benzothiazoles Disease Models, Animal Drug Therapy, Combination Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometrium Endometrium Endometrium Endometrium

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