Skip to main content

Advertisement

SpringerLink
Log in

Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology

  • Original Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Two hallmarks of chronic multiple sclerosis lesions are the absence of significant spontaneous remyelination and primary as well as secondary neurodegeneration. Both characteristics may be influenced by the presence of inhibitory factors preventing myelin and neuronal repair. We investigated the potential of antibodies against Nogo-A, a well-known inhibitory protein for neuronal growth and plasticity, to enhance neuronal regeneration and remyelination in two animal models of multiple sclerosis. We induced a targeted experimental autoimmune encephalomyelitis (EAE) lesion in the dorsal funiculus of the cervical spinal cord of adult rats resulting in a large drop of skilled forelimb motor functions. We subsequently observed improved recovery of forelimb function after anti-Nogo-A treatment. Anterograde tracing of the corticospinal tract revealed enhanced axonal sprouting and arborisation within the spinal cord gray matter preferentially targeting pre-motor and motor spinal cord laminae on lesion level and above in the anti-Nogo-A-treated animals. An important additional effect of Nogo-A-neutralization was enhanced remyelination observed after lysolecithin-induced demyelination of spinal tracts. Whereas remyelinated fiber numbers in the lesion site were increased several fold, no effect of Nogo-A-inhibition was observed on oligodendrocyte precursor proliferation, migration, or differentiation. Enhancing remyelination and promoting axonal regeneration and plasticity represent important unmet medical needs in multiple sclerosis. Anti-Nogo-A antibodies hold promise as a potential new therapy for multiple sclerosis, in particular during the chronic phase of the disease when neurodegeneration and remyelination failure determine disability evolution.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Amor S, Baker D (2012) Checklist for reporting and reviewing studies of experimental animal models of multiple sclerosis and related disorders. Mult Scler Relat Disord 1:111–115. doi:10.1016/j.msard.2012.01.003

    Article  PubMed  Google Scholar 

  2. Blakemore WF, Franklin RJ (2008) Remyelination in experimental models of toxin-induced demyelination. Curr Top Microbiol Immunol 318:193–212

    CAS  PubMed  Google Scholar 

  3. Chong SY, Rosenberg SS, Fancy SP, Zhao C, Shen YA, Hahn AT, McGee AW, Xu X, Zheng B, Zhang LI et al (2012) Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination. Proc Natl Acad Sci USA 109:1299–1304. doi:10.1073/pnas.1113540109

    Article  CAS  PubMed  Google Scholar 

  4. Daams M, Steenwijk MD, Wattjes MP, Geurts JJ, Uitdehaag BM, Tewarie PK, Balk LJ, Pouwels PJ, Killestein J, Barkhof F (2015) Unraveling the neuroimaging predictors for motor dysfunction in long-standing multiple sclerosis. Neurology 85:248–255. doi:10.1212/wnl.0000000000001756

    Article  PubMed  Google Scholar 

  5. Diaz E, Morales H (2016) Spinal cord anatomy and clinical syndromes. Semin Ultrasound CT MR 37:360–371. doi:10.1053/j.sult.2016.05.002

    Article  PubMed  Google Scholar 

  6. Dubois-Dalcq M, Ffrench-Constant C, Franklin RJ (2005) Enhancing central nervous system remyelination in multiple sclerosis. Neuron 48:9–12. doi:10.1016/j.neuron.2005.09.004

    Article  CAS  PubMed  Google Scholar 

  7. Feinstein A, Freeman J, Lo AC (2015) Treatment of progressive multiple sclerosis: what works, what does not, and what is needed. Lancet Neurol 14:194–207. doi:10.1016/s1474-4422(14)70231-5

    Article  PubMed  Google Scholar 

  8. Ferguson B, Matyszak MK, Esiri MM, Perry VH (1997) Axonal damage in acute multiple sclerosis lesions. Brain J Neurol 120(Pt 3):393–399

    Article  Google Scholar 

  9. Fontoura P, Ho PP, DeVoss J, Zheng B, Lee BJ, Kidd BA, Garren H, Sobel RA, Robinson WH, Tessier-Lavigne M et al (2004) Immunity to the extracellular domain of Nogo-A modulates experimental autoimmune encephalomyelitis. J Immunol (Baltimore, Md: 1950) 173:6981–6992

    Article  CAS  Google Scholar 

  10. Franklin RJ, Ffrench-Constant C (2008) Remyelination in the CNS: from biology to therapy. Nat Rev Neurosci 9:839–855. doi:10.1038/nrn2480

    Article  CAS  PubMed  Google Scholar 

  11. Franklin RJ, Ffrench-Constant C, Edgar JM, Smith KJ (2012) Neuroprotection and repair in multiple sclerosis. Nat Rev Neurol 8:624–634. doi:10.1038/nrneurol.2012.200

    Article  PubMed  Google Scholar 

  12. Franklin RJ, Gallo V (2014) The translational biology of remyelination: past, present, and future. Glia 62:1905–1915. doi:10.1002/glia.22622

    Article  PubMed  Google Scholar 

  13. Fry EJ, Ho C, David S (2007) A role for Nogo receptor in macrophage clearance from injured peripheral nerve. Neuron 53:649–662. doi:10.1016/j.neuron.2007.02.009

    Article  CAS  PubMed  Google Scholar 

  14. Funfschilling U, Supplie LM, Mahad D, Boretius S, Saab AS, Edgar J, Brinkmann BG, Kassmann CM, Tzvetanova ID, Mobius W et al (2012) Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature 485:517–521. doi:10.1038/nature11007

    PubMed  PubMed Central  Google Scholar 

  15. Huang JY, Wang YX, Gu WL, Fu SL, Li Y, Huang LD, Zhao Z, Hang Q, Zhu HQ, Lu PH (2012) Expression and function of myelin-associated proteins and their common receptor NgR on oligodendrocyte progenitor cells. Brain Res 1437:1–15. doi:10.1016/j.brainres.2011.12.008

    Article  CAS  PubMed  Google Scholar 

  16. Ineichen BV, Plattner PS, Good N, Martin R, Linnebank M, Schwab ME (2017) Nogo-A antibodies for progressive multiple sclerosis. CNS Drugs 31:187–198

    Article  CAS  PubMed  Google Scholar 

  17. Ineichen BV, Schnell L, Gullo M, Kaiser J, Schneider MP, Mosberger AC, Good N, Linnebank M, Schwab ME (2017) Direct, long-term intrathecal application of therapeutics to the rodent CNS. Nat Protoc 12:104–131. doi:10.1038/nprot.2016.151

    Article  CAS  PubMed  Google Scholar 

  18. Ineichen BV, Weinmann O, Good N, Plattner P, Wicki C, Rushing EJ, Linnebank M, Schwab ME (2016) Sudan black: a fast, easy, and non-toxic method to assess myelin repair in demyelinating diseases. Neuropathol Appl Neurobiol. doi:10.1111/nan.12373

    Google Scholar 

  19. Irvine KA, Blakemore WF (2008) Remyelination protects axons from demyelination-associated axon degeneration. Brain J Neurol 131:1464–1477. doi:10.1093/brain/awn080

    Article  CAS  Google Scholar 

  20. Karnezis T, Mandemakers W, McQualter JL, Zheng B, Ho PP, Jordan KA, Murray BM, Barres B, Tessier-Lavigne M, Bernard CC (2004) The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination. Nat Neurosci 7:736–744. doi:10.1038/nn1261

    Article  CAS  PubMed  Google Scholar 

  21. Kempf A, Tews B, Arzt ME, Weinmann O, Obermair FJ, Pernet V, Zagrebelsky M, Delekate A, Iobbi C, Zemmar A et al (2014) The sphingolipid receptor S1PR2 is a receptor for Nogo-a repressing synaptic plasticity. PLoS Biol 12:e1001763. doi:10.1371/journal.pbio.1001763

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kerschensteiner M, Bareyre FM, Buddeberg BS, Merkler D, Stadelmann C, Bruck W, Misgeld T, Schwab ME (2004) Remodeling of axonal connections contributes to recovery in an animal model of multiple sclerosis. J Exp Med 200:1027–1038. doi:10.1084/jem.20040452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kerschensteiner M, Stadelmann C, Buddeberg BS, Merkler D, Bareyre FM, Anthony DC, Linington C, Bruck W, Schwab ME (2004) Targeting experimental autoimmune encephalomyelitis lesions to a predetermined axonal tract system allows for refined behavioral testing in an animal model of multiple sclerosis. Am J Pathol 164:1455–1469. doi:10.1016/S0002-9440(10)63232-4

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 8:e1000412. doi:10.1371/journal.pbio.1000412

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kotter MR, Setzu A, Sim FJ, Van Rooijen N, Franklin RJ (2001) Macrophage depletion impairs oligodendrocyte remyelination following lysolecithin-induced demyelination. Glia 35:204–212

    Article  CAS  PubMed  Google Scholar 

  26. Kotter MR, Zhao C, van Rooijen N, Franklin RJ (2005) Macrophage-depletion induced impairment of experimental CNS remyelination is associated with a reduced oligodendrocyte progenitor cell response and altered growth factor expression. Neurobiol Dis 18:166–175. doi:10.1016/j.nbd.2004.09.019

    Article  CAS  PubMed  Google Scholar 

  27. Lee JY, Petratos S (2013) Multiple sclerosis: does Nogo play a role? Neurosci Rev J bringing Neurobiol Neurol Psychiatry 19:394–408. doi:10.1177/1073858413477207

    Google Scholar 

  28. Liebscher T, Schnell L, Schnell D, Scholl J, Schneider R, Gullo M, Fouad K, Mir A, Rausch M, Kindler D et al (2005) Nogo-A antibody improves regeneration and locomotion of spinal cord-injured rats. Ann Neurol 58:706–719. doi:10.1002/ana.20627

    Article  CAS  PubMed  Google Scholar 

  29. Ma Z, Cao Q, Zhang L, Hu J, Howard RM, Lu P, Whittemore SR, Xu XM (2009) Oligodendrocyte precursor cells differentially expressing Nogo-A but not MAG are more permissive to neurite outgrowth than mature oligodendrocytes. Exp Neurol 217:184–196. doi:10.1016/j.expneurol.2009.02.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mahad DH, Trapp BD, Lassmann H (2015) Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol 14:183–193. doi:10.1016/s1474-4422(14)70256-x

    Article  CAS  PubMed  Google Scholar 

  31. Maier IC, Baumann K, Thallmair M, Weinmann O, Scholl J, Schwab ME (2008) Constraint-induced movement therapy in the adult rat after unilateral corticospinal tract injury. J Neurosci Off J Soc Neurosci 28:9386–9403. doi:10.1523/jneurosci.1697-08.2008

    Article  CAS  Google Scholar 

  32. Mei F, Fancy SP, Shen YA, Niu J, Zhao C, Presley B, Miao E, Lee S, Mayoral SR, Redmond SA et al (2014) Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis. Nat Med 20:954–960. doi:10.1038/nm.3618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Metz GA, Whishaw IQ (2002) Cortical and subcortical lesions impair skilled walking in the ladder rung walking test: a new task to evaluate fore- and hindlimb stepping, placing, and co-ordination. J Neurosci Methods 115:169–179

    Article  PubMed  Google Scholar 

  34. Mi S, Lee X, Shao Z, Thill G, Ji B, Relton J, Levesque M, Allaire N, Perrin S, Sands B et al (2004) LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat Neurosci 7:221–228

    Article  CAS  PubMed  Google Scholar 

  35. Mi S, Miller RH, Tang W, Lee X, Hu B, Wu W, Zhang Y, Shields CB, Zhang Y, Miklasz S et al (2009) Promotion of central nervous system remyelination by induced differentiation of oligodendrocyte precursor cells. Ann Neurol 65:304–315. doi:10.1002/ana.21581

    Article  CAS  PubMed  Google Scholar 

  36. Miron VE, Zehntner SP, Kuhlmann T, Ludwin SK, Owens T, Kennedy TE, Bedell BJ, Antel JP (2009) Statin therapy inhibits remyelination in the central nervous system. Am J Pathol 174:1880–1890. doi:10.2353/ajpath.2009.080947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Montoya CP, Campbell-Hope LJ, Pemberton KD, Dunnett SB (1991) The “staircase test”: a measure of independent forelimb reaching and grasping abilities in rats. J Neurosci Methods 36:219–228

    Article  CAS  PubMed  Google Scholar 

  38. Oertle T, van der Haar ME, Bandtlow CE, Robeva A, Burfeind P, Buss A, Huber AB, Simonen M, Schnell L, Brosamle C et al (2003) Nogo-A inhibits neurite outgrowth and cell spreading with three discrete regions. J Neurosci Off J Soc Neurosci 23:5393–5406

    CAS  Google Scholar 

  39. Ontaneda D, Fox RJ, Chataway J (2015) Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives. Lancet Neurol 14:208–223. doi:10.1016/s1474-4422(14)70264-9

    Article  PubMed  PubMed Central  Google Scholar 

  40. Organization WH (2008) Multiple Sclerosis International Federation. Atlas: Multiple Sclerosis Resources in the World 2008. World Health Organization, Geneva, pp 13–17

    Google Scholar 

  41. Petratos S, Ozturk E, Azari MF, Kenny R, Lee JY, Magee KA, Harvey AR, McDonald C, Taghian K, Moussa L et al (2012) Limiting multiple sclerosis related axonopathy by blocking Nogo receptor and CRMP-2 phosphorylation. Brain J Neurol 135:1794–1818. doi:10.1093/brain/aws100

    Article  Google Scholar 

  42. Pourabdolhossein F, Mozafari S, Morvan-Dubois G, Mirnajafi-Zadeh J, Lopez-Juarez A, Pierre-Simons J, Demeneix BA, Javan M (2014) Nogo receptor inhibition enhances functional recovery following lysolecithin-induced demyelination in mouse optic chiasm. PLoS ONE 9:e106378. doi:10.1371/journal.pone.0106378

    Article  PubMed  PubMed Central  Google Scholar 

  43. Reindl M, Khantane S, Ehling R, Schanda K, Lutterotti A, Brinkhoff C, Oertle T, Schwab ME, Deisenhammer F, Berger T et al (2003) Serum and cerebrospinal fluid antibodies to Nogo-A in patients with multiple sclerosis and acute neurological disorders. J Neuroimmunol 145:139–147

    Article  CAS  PubMed  Google Scholar 

  44. Salic A, Mitchison TJ (2008) A chemical method for fast and sensitive detection of DNA synthesis in vivo. Proc Natl Acad Sci USA 105:2415–2420. doi:10.1073/pnas.0712168105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Sasaki M, Lankford KL, Brown RJ, Ruddle NH, Kocsis JD (2010) Focal experimental autoimmune encephalomyelitis in the Lewis rat induced by immunization with myelin oligodendrocyte glycoprotein and intraspinal injection of vascular endothelial growth factor. Glia 58:1523–1531. doi:10.1002/glia.21026

    Article  PubMed  Google Scholar 

  46. Satoh J, Onoue H, Arima K, Yamamura T (2005) Nogo-A and nogo receptor expression in demyelinating lesions of multiple sclerosis. J Neuropathol Exp Neurol 64:129–138

    Article  CAS  PubMed  Google Scholar 

  47. Schwab ME (2010) Functions of Nogo proteins and their receptors in the nervous system. Nat Rev Neurosci 11:799–811. doi:10.1038/nrn2936

    Article  CAS  PubMed  Google Scholar 

  48. Schwab ME, Strittmatter SM (2014) Nogo limits neural plasticity and recovery from injury. Curr Opin Neurobiol 27:53–60. doi:10.1016/j.conb.2014.02.011

    Article  CAS  PubMed  Google Scholar 

  49. Stadelmann C (2011) Multiple sclerosis as a neurodegenerative disease: pathology, mechanisms and therapeutic implications. Curr Opin Neurol 24:224–229. doi:10.1097/WCO.0b013e328346056f

    Article  CAS  PubMed  Google Scholar 

  50. Steward O, Willenberg R (2016) Rodent spinal cord injury models for studies of axon regeneration. Exp Neurol. doi:10.1016/j.expneurol.2016.06.029

    PubMed Central  Google Scholar 

  51. Theotokis P, Lourbopoulos A, Touloumi O, Lagoudaki R, Kofidou E, Nousiopoulou E, Poulatsidou KN, Kesidou E, Tascos N, Spandou E et al (2012) Time course and spatial profile of Nogo-A expression in experimental autoimmune encephalomyelitis in C57BL/6 mice. J Neuropathol Exp Neurol 71:907–920. doi:10.1097/NEN.0b013e31826caebe

    Article  CAS  PubMed  Google Scholar 

  52. Tomassini V, d’Ambrosio A, Petsas N, Wise RG, Sbardella E, Allen M, Tona F, Fanelli F, Foster C, Carni M et al (2016) The effect of inflammation and its reduction on brain plasticity in multiple sclerosis: MRI evidence. Hum Brain Mapp 37:2431–2445. doi:10.1002/hbm.23184

    Article  PubMed  PubMed Central  Google Scholar 

  53. Trapp BD, Nave KA (2008) Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci 31:247–269. doi:10.1146/annurev.neuro.30.051606.094313

    Article  CAS  PubMed  Google Scholar 

  54. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L (1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338:278–285. doi:10.1056/NEJM199801293380502

    Article  CAS  PubMed  Google Scholar 

  55. Wahl AS, Omlor W, Rubio JC, Chen JL, Zheng H, Schroter A, Gullo M, Weinmann O, Kobayashi K, Helmchen F et al (2014) Neuronal repair. Asynchronous therapy restores motor control by rewiring of the rat corticospinal tract after stroke. Science (New York, NY) 344:1250–1255. doi:10.1126/science.1253050

    Article  CAS  Google Scholar 

  56. Weinmann O, Schnell L, Ghosh A, Montani L, Wiessner C, Wannier T, Rouiller E, Mir A, Schwab ME (2006) Intrathecally infused antibodies against Nogo-A penetrate the CNS and downregulate the endogenous neurite growth inhibitor Nogo-A. Mol Cell Neurosci 32:161–173. doi:10.1016/j.mcn.2006.03.007

    Article  CAS  PubMed  Google Scholar 

  57. Weinshenker BG (1998) The natural history of multiple sclerosis: update 1998. Semin Neurol 18:301–307. doi:10.1055/s-2008-1040881

    Article  CAS  PubMed  Google Scholar 

  58. Woodruff RH, Franklin RJ (1999) Demyelination and remyelination of the caudal cerebellar peduncle of adult rats following stereotaxic injections of lysolecithin, ethidium bromide, and complement/anti-galactocerebroside: a comparative study. Glia 25:216–228

    Article  CAS  PubMed  Google Scholar 

  59. Wootla B, Denic A, Watzlawik JO, Warrington AE, Rodriguez M (2015) Antibody-Mediated Oligodendrocyte Remyelination Promotes Axon Health in Progressive Demyelinating Disease

  60. Wujek JR, Bjartmar C, Richer E, Ransohoff RM, Yu M, Tuohy VK, Trapp BD (2002) Axon loss in the spinal cord determines permanent neurological disability in an animal model of multiple sclerosis. J Neuropathol Exp Neurol 61:23–32

    Article  PubMed  Google Scholar 

  61. Yang Y, Liu Y, Wei P, Peng H, Winger R, Hussain RZ, Ben LH, Cravens PD, Gocke AR, Puttaparthi K et al (2010) Silencing Nogo-A promotes functional recovery in demyelinating disease. Ann Neurol 67:498–507. doi:10.1002/ana.21935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank the assistance and support of the Center for Microscopy and Image Analysis for support with the Axio Scan Slidescanner. We thank SJ. Feinberg and L. Godowsky for help with surgery.

Author information

Author notes

  1. Michael Linnebank

    Present address: Department of Neurorehabilitation, School of Medicine, HELIOS Klinik Hagen-Ambrock, Witten/Herdecke University Faculty of Health, Ambrocker Weg 60, 58091, Hagen, Germany

  2. Christiane Bleul

    Present address: Translational Genomics Research Institute, Phoenix, AZ, USA

  3. Benjamin V. Ineichen and Sandra Kapitza contributed equally and share the first authorship.

  4. Michael Linnebank and Martin E. Schwab contributed equally and share the senior authorship.

Authors and Affiliations

  1. Brain Research Institute, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland

    Benjamin V. Ineichen, Sandra Kapitza, Christiane Bleul, Nicolas Good, Patricia S. Plattner, Maryam S. Seyedsadr, Julia Kaiser, Marc P. Schneider, Björn Zörner & Martin E. Schwab

  2. Department of Health Sciences and Technology, ETH Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland

    Benjamin V. Ineichen, Sandra Kapitza, Nicolas Good, Patricia S. Plattner, Maryam S. Seyedsadr, Julia Kaiser, Marc P. Schneider, Björn Zörner & Martin E. Schwab

  3. Department of Neurology, University Hospital of Zurich, Zurich, Switzerland

    Benjamin V. Ineichen, Sandra Kapitza, Maryam S. Seyedsadr, Julia Kaiser, Roland Martin & Michael Linnebank

Authors
  1. Benjamin V. Ineichen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sandra Kapitza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christiane Bleul
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nicolas Good
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Patricia S. Plattner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maryam S. Seyedsadr
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Julia Kaiser
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marc P. Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Björn Zörner
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Roland Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Michael Linnebank
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Martin E. Schwab
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

BVI, MES, CB, SK, BZ, and ML contributed to the conceptual development; BVI, CB, MPS, and SK did the targeted EAE surgery, BVI, CB, and NG analyzed data from the targeted EAE experiments; BVI, PSP, NG, MSM, and JK carried out and analyzed all experiments using lysolecithin; BVI compiled figures, BVI and MES wrote the manuscript, and ML and RM provided critical input on the manuscript.

Corresponding author

Correspondence to Benjamin V. Ineichen.

Ethics declarations

Funding

We are thankful for funding from the Swiss National Science Foundation (grant no. 31003A-149315-1 to MES), the Christopher and Dana Reeve Foundation (to MES), the Swiss MS Society, the Hartmann-Müller Foundation, Zurich, the Desirée-and-Niels-Yde Foundation (to BVI) and an MD-PhD fellowship of the Swiss National Science Foundation (No. 323530_151488, to BVI).

Conflict of interest

MES is a founder and board member of the University of Zurich spin-off company NovaGo Therapeutics Inc. seeking at developing Nogo-A-neutralizing therapies. RM is supported by the Clinical Research Priority Project MS of the University Zurich. BVI, SK, CB, NG, PSP, MSM, JK, MPS, ML, and BZ declare no conflict of interest.

Ethical standards

For all studies including animals, all applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All animal procedures and protocols were approved by the Veterinary Office of the Canton of Zurich, Switzerland. This study is written in accordance with the adapted ARRIVE guidelines for reporting of studies using MS animal models [1, 24].

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ineichen, B.V., Kapitza, S., Bleul, C. et al. Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology. Acta Neuropathol 134, 423–440 (2017). https://doi.org/10.1007/s00401-017-1745-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-017-1745-3

Keywords

Search

Navigation