Nature Communications 2014-01-01

Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis.

K Sugihara, Y Kobayashi, A Suzuki, N Tamura, K Motamedchaboki, C-T Huang, T O Akama, J Pecotte, P Frost, C Bauer, J B Jimenez, J Nakayama, D Aoki, M N Fukuda

Index: Nat. Commun. 5 , 4478, (2014)

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Abstract

Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. As most endometriosis occurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated channel β3, a sorting pathway protein. We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans.