Functional activity of anti-LINGO-1 antibody opicinumab requires target engagement at a secondary binding site

References

• Mi S, Lee X, Shao Z, Thill G, Ji B, Relton J, Levesque M, Allaire N, Perrin S, Sands B, et al. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat Neurosci. 2004;7(3):221–14. doi:https://doi.org/10.1038/nn1188.
   PubMed Web of Science ®Google Scholar
• Mi S, Miller RH, Lee X, Scott ML, Shulag-Morskaya S, Shao Z, Chang J, Thill G, Levesque M, Zhang M, et al. LINGO-1 negatively regulates myelination by oligodendrocytes. Nat Neurosci. 2005;8:745–51. doi:https://doi.org/10.1038/nn1460.
   PubMed Web of Science ®Google Scholar
• Mi S, Pepinsky RB, Cadavid D. Blocking LINGO-1 as a therapy to promote CNS repair: from concept to the clinic. Mol Cell Neurosci. 2013;60:36–42. doi:https://doi.org/10.1016/j.mcn.2014.02.006.
   Google Scholar
• Andrews JL, Fernandez-Enright F. A decade from discovery to therapy: lingo-1, the dark horse in neurological and psychiatric disorders. Neurosci Biobehav Rev. 2015;56:97–114. doi:https://doi.org/10.1016/j.neubiorev.2015.06.009.
   PubMed Web of Science ®Google Scholar
• Inoue H, Lin L, Lee X, Shao Z, Mendes S, Snodgrass-Belt P, Sweigard H, Engber T, Pepinsky B, Yang L, et al. Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson’s disease models. Proc Natl Acad Sci U S A. 2007;104(36):14430–35. doi:https://doi.org/10.1073/pnas.0700901104.
   PubMed Web of Science ®Google Scholar
• Fu QL, Hu B, Wu W, Pepinsky RB, Mi S, So KF. Blocking LINGO-1 function promotes retinal ganglion cell survival following ocular hypertension and optic nerve transection. Invest Ophthalmol Vis Sci. 2008;49:975–85. doi:https://doi.org/10.1167/iovs.07-1199.
   PubMed Web of Science ®Google Scholar
• Mi S, Hu B, Hahm K, Luo Y, Kam Hui ES, Yuan Q, Wong WM, Wang L, Su H, Chu TH, et al. LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis. Nat Med. 2007;13:1228–33. doi:https://doi.org/10.1038/nm1664.
   PubMed Web of Science ®Google Scholar
• Mi S, Miller RH, Tang W, Lee X, Hu B, Wu W, Zhang Y, Shields CB, Zhang Y, Miklasz S, et al. Promotion of central nervous system remyelination by induced differentiation of oligodendrocyte precursor cells. Ann Neurol. 2009;65:304–15. doi:https://doi.org/10.1002/ana.v65:3.
   PubMed Web of Science ®Google Scholar
• Zhang ZH, Li JJ, Wang QJ, Zhao WQ, Hong J, Lou SJ, Xu XH. WNK1 is involved in Nogo66 inhibition of OPC differentiation. Mol Cell Neurosci. 2015;65:135–42. doi:https://doi.org/10.1016/j.mcn.2015.03.003.
   PubMed Web of Science ®Google Scholar
• Gresle MM, Liu Y, Kilpatrick TJ, Kemper D, Wu QZ, Hu B, Fu QL, So KF, Sheng G, Huang G, et al. Blocking LINGO-1 in vivo reduces degeneration and enhances regeneration of the optic nerve. Mult Scler J Exp Transl Clin. 2016;2:2055217316641704. doi:https://doi.org/10.1177/2055217316641704.
   Google Scholar
• Ji B, Li M, Wu WT, Yick LW, Lee X, Shao Z, Wang J, So KF, McCoy JM, Pepinsky RB, et al. LINGO-1 antagonist promotes functional recovery and axonal sprouting after spinal cord injury. Mol Cell Neurosci. 2006;33:311–20. doi:https://doi.org/10.1016/j.mcn.2006.08.003.
   PubMed Web of Science ®Google Scholar
• Pepinsky RB, Shao Z, Ji B, Wang Q, Meng G, Walus L, Lee X, Hu Y, Graff C, Garber E, et al. Exposure levels of anti-LINGO-1 Li81 antibody in the central nervous system and dose-efficacy relationships in rat spinal cord remyelination models after systemic administration. J Pharmacol Exp Ther. 2011;339:519–29. doi:https://doi.org/10.1124/jpet.111.183483.
   PubMed Web of Science ®Google Scholar
• Cen J, Wu H, Wang J, Ren X, Zhang H, Wang J, Wan Y, Deng Y. Local injection of lentivirus encoding LINGO-1 shRNA promotes functional recovery in rats with complete spinal cord transaction. Spine. 2013 Sep 1;38(19):1632–39. doi:https://doi.org/10.1097/BRS.0b013e31829dd58f.
   PubMed Web of Science ®Google Scholar
• Youssef AEH, Dief AE, El Azhary NM, Abdelmonsif DA, El-Fetiany OS. LINGO-1 siRNA nanoparticles promote central remyelination in ethidium bromide-induced demyelination in rats. J Physiol Biochem. 2019;75(1):89–99. doi:https://doi.org/10.1007/s13105-018-00660-6.
   PubMed Web of Science ®Google Scholar
• Mosyak L, Wood A, Dwyer B, Buddha M, Johnson M, Aulabaugh A, Zhong X, Presman E, Benard S, Kelleher K, et al. The structure of the Lingo-1 ectodomain, a module implicated in central nervous system repair inhibition. J Biol Chem. 2006;281:36378–90. doi:https://doi.org/10.1074/jbc.M607314200.
   PubMed Web of Science ®Google Scholar
• Mi S, McCoy J, Pepinsky RB, Lee DHS, Inventors; Biogen Idec, Inc., Assignee. 2010. Nogo receptor binding protein. United States patent US 7,785,829.
   Google Scholar
• Bourikas D, Mir A, Walmsley AR. LINGO-1-mediated inhibition of oligodendrocyte differentiation does not require the leucine-rich repeats and is reversed by p75(NTR) antagonists. Mol Cell Neurosci. 2010;45:363–69. doi:https://doi.org/10.1016/j.mcn.2010.07.009.
   PubMed Web of Science ®Google Scholar
• Kaplon H, Muralidharan M, Schneider Z, Reichert JM. Antibodies to watch in 2020. MABS. 2020;12(1):e1703531. doi:https://doi.org/10.1080/19420862.2019.1703531.
   PubMed Web of Science ®Google Scholar
• Ecker DM, Jones SD, Levine HL. The therapeutic monoclonal antibody market. MAbs. 2015;7(1):9–14. doi:https://doi.org/10.4161/19420862.2015.989042.
   PubMed Web of Science ®Google Scholar
• Pepinsky RB, Arndt JW, Quan C, Gao Y, Quintero-Monzon O, Lee X, Mi S. Structure of the LINGO-1-anti-LINGO-1 Li81 antibody complex provides insights into the biology of LINGO-1 and the mechanism of action of the antibody therapy. J Pharmacol Exp Ther. 2014;350:110–23. doi:https://doi.org/10.1124/jpet.113.211771.
   PubMed Web of Science ®Google Scholar
• Cadavid D, Balcer L, Galetta S, Aktas O, Ziemssen T, Vanopdenbosch L, Frederiksen J, Skeen M, Jaffe GJ, Butzkueven H, et al. Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2017;16(3):189–99. doi:https://doi.org/10.1016/S1474-4422(16)30377-5.
   PubMed Web of Science ®Google Scholar
• Klistorner A, Chai Y, Leocani L, Albrecht P, Aktas O, Butzkueven H, Ziemssen T, Ziemssen F, Frederiksen J, Xu L, et al. Assessment of opicinumab in acute optic neuritis using multifocal visual evoked potential. CNS Drugs. 2018;32(12):1159–71. doi:https://doi.org/10.1007/s40263-018-0575-8.
   PubMed Web of Science ®Google Scholar
• Molecular Operating Environment (MOE) software. 2016. 0801; Chemical Computing Group ULC, 1010 Sherbrooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7, 2018.
   Google Scholar
• Mi S, Pepinsky RB, Graff C, Inventors; Biogen Idec, Inc., Assignee. 2017. Compositions comprising antibodies to LINGO or fragments thereof. United States patent US 9,745,375.
   Google Scholar
• Baldassari LE, Feng J, Clayton BLL, Oh SH, Sakaie K, Tesar PJ, Wang Y, Cohen JA. Developing therapeutic strategies to promote myelin repair in multiple sclerosis. Expert Rev Neurother. 2019;19(10):997–1013. doi:https://doi.org/10.1080/14737175.2019.1632192.
   PubMed Web of Science ®Google Scholar
• Town J, Pais H, Harrison S, Stead LF, Bataille C, Bunjobpol W, Zhang J, Rabbitts TH. Exploring the surfaceome of ewing sarcoma identifies a new and unique therapeutic target. Proc Natl Acad Sci U S A. 2016;113(13):3603–08. doi:https://doi.org/10.1073/pnas.1521251113.
   PubMed Web of Science ®Google Scholar
• Meabon JS, De Laat R, Ieguchi K, Wiley JC, Hudson MP, Bothwell M. LINGO-1 protein interacts with the p75 neurotrophin receptor in intracellular membrane compartments. J Biol Chem. 2015;290(15):9511–20. doi:https://doi.org/10.1074/jbc.M114.608018.
   PubMed Web of Science ®Google Scholar
• Meabon JS, de Laat R, Ieguchi K, Serbzhinsky D, Hudson MP, Huber BR, Wiley JC, Bothwell M. Intracellular LINGO-1 negatively regulates Trk neurotrophin receptor signaling. Mol Cell Neurosci. 2016;70:1–10. doi:https://doi.org/10.1016/j.mcn.2015.11.002.
   PubMed Web of Science ®Google Scholar
• Massol RH, Boll W, Griffin AM, Kirchhausen T. A burst of auxilin recruitment determines the onset of clathrin-coated vesicle uncoating. Proc Natl Acad Sci U S A. 2006;103(27):10265–70. doi:https://doi.org/10.1073/pnas.0603369103.
   PubMed Web of Science ®Google Scholar
• Manders EMM, Stap J, Brakenhoff GJ, van Driel R, Aten JA. Dynamics of three-dimensional replication patterns during the S-phase, analysed by double labelling of DNA and confocal microscopy. J Cell Sci. 1992;103:857–62.
   PubMed Web of Science ®Google Scholar