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

Nat Commun. 2014 Jul 22:5:4478. doi: 10.1038/ncomms5478.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / drug effects*
  • Cyclic Nucleotide-Gated Cation Channels / metabolism
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Drug Evaluation, Preclinical / methods
  • Endometriosis / drug therapy*
  • Endometriosis / pathology
  • Endometrium / pathology
  • Epithelial Cells / metabolism
  • Female
  • Humans
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Molecular Targeted Therapy / methods*
  • Papio
  • Peptide Library
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Peritoneal Diseases / drug therapy
  • Peritoneal Diseases / pathology

Substances

  • CNGB3 protein, human
  • Cyclic Nucleotide-Gated Cation Channels
  • DNA-Binding Proteins
  • Peptide Library
  • Peptides
  • ZNF473 protein, human