Skip to main content

Advertisement

SpringerLink
Log in

Recent clinical trials and future therapies

  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Immunotherapy for multiple sclerosis (MS) has developed extremely successfully during the past decade and a number of new strategies were developed for the treatment of the disease. Examples include therapeutic strategies targeting leukocyte differentiation molecules, costimulatory molecules, anti-adhesion molecules, chemotaxis, novel immunomodulators, autologous stem cell transplantation, anti-infectious therapies and strategies for neuroprotection, neurorepair and remyelination. Here we describe examples of monoclonal antibodies, a novel immunosuppressant and interesting neuroprotective strategies.

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

Similar content being viewed by others

References

  1. Bar-Or A, Calabresi PA, Arnlod D,Markowitz C, Shafer S, Kasper LH,Waubant E, Gazda S, Fox RJ, PanzaraM, Sarkar N, Agarwal S, Smith CH(2008) Rituximab in relapsing-remittingmultiple sclerosis: a 72-week,open-label, phase I trial. Ann Neurol63:395–400

    Article  PubMed  CAS  Google Scholar 

  2. Beutler E (1992) Cladribine (2-chlorodeoxyadenosine).Lancet 340:952–956

    Article  PubMed  CAS  Google Scholar 

  3. Beutler E, Sipe JC, Romine JS, KoziolJA, McMillan R, Zyroff J (1996) Thetreatment of chronic progressivemultiple sclerosis with cladribine. ProcNatl Acad Sci USA 93:1716–1720

    Article  CAS  Google Scholar 

  4. Bielekova B, Catalfamo M, Reichert-Scrivner S, Packer A, Cerna M, WaldmannTA, McFarland H, Henkart PA,Martin R (2006) RegulatoryCD56(bright) natural killer cells mediateimmunomodulatory effects ofIL-2Ralpha-targeted therapy (daclizumab)in multiple sclerosis. Proc NatlAcad Sci USA 103:5941–5946

    Article  CAS  Google Scholar 

  5. Bielekova B, Richert N, Howard T,Blevins G, Markovic-Plese S, McCartinJ, Frank JA, Wurfel J, Ohayon J, WaldmannTA, McFarland HF, Martin R(2004) Humanized anti-CD25 (daclizumab)inhibits disease activity inmultiple sclerosis patients failing torespond to interferon beta. Proc NatlAcad Sci USA 101:8705–8708

    Article  CAS  Google Scholar 

  6. Brinkmann V, Davis MD, Heise CE,Albert R, Cottens S, Hof R, Bruns C,Prieschl E, Baumruker T, Hiestand P,Foster CA, Zollinger M, Lynch KR(2002) The immune modulatorFTY720 targets sphingosine 1-phosphatereceptors. J Biol Chem 277:21453–21457

    Article  PubMed  CAS  Google Scholar 

  7. Chiba K (2005) FTY720, a new class ofimmunomodulator, inhibits lymphocyteegress from secondary lymphoidtissues and thymus by agonistic activityat sphingosine 1-phosphate receptors.Pharmacol Ther 108:308–319

    Article  PubMed  CAS  Google Scholar 

  8. Coles A, Group TCS (2007) Efficacy ofAlemtuzumab in Treatment-NaiveRelapsing-Remitting Multiple Sclerosis:Analysis after Two Years of StudyCAMMS223. Neurology 68(Suppl 1):A100

    Google Scholar 

  9. Coles AJ, Wing M, Smith S, Coraddu F,Greer S, Taylor C, Weetman A, Hale G,Chatterjee VK, Waldmann H, CompstonA (1999) Pulsed monoclonal antibodytreatment and autoimmune thyroiddisease in multiple sclerosis.Lancet 354:1691–1695

    Article  PubMed  CAS  Google Scholar 

  10. Coles AJ, Wing MG, Molyneux P,Paolillo A, Davie CM, Hale G, Miller D,Waldmann H, Compston A (1999)Monoclonal antibody treatment exposesthree mechanisms underlyingthe clinical course of multiple sclerosis.Ann Neurol 46:296–304

    Article  PubMed  CAS  Google Scholar 

  11. Filippi M, Rovaris M, Iannucci G,Mennea S, Sormani MP, Comi G (2000)Whole brain volume changes in patientswith progressive MS treated withcladribine. Neurology 55:1714–1718

    PubMed  CAS  Google Scholar 

  12. Filippi M, Rovaris M, Rice GP, SormaniMP, Iannucci G, Giacomotti L, Comi G(2000) The effect of cladribine on T(1)’black hole’ changes in progressive MS.J Neurol Sci 176:42–44

    Article  PubMed  CAS  Google Scholar 

  13. Fujino M, Funeshima N, Kitazawa Y,Kimura H, Amemiya H, Suzuki S, LiXK (2003) Amelioration of experimentalautoimmune encephalomyelitis inLewis rats by FTY720 treatment.J Pharmacol Exp Ther 305:70–77

    Article  PubMed  CAS  Google Scholar 

  14. Hauser SL, Waubant E, Arnold DL,Vollmer T, Antel J, Fox RJ, Bar-Or A,Panzara M, Sarkar N, Agarwal S,Langer-Gould A, Smith CH (2008) B-celldepletion with rituximab in relapsing-remitting multiple sclerosis.N Engl J Med 358:676–688

    Article  PubMed  CAS  Google Scholar 

  15. Hohlfeld R, Wekerle H (2004) Autoimmuneconcepts of multiple sclerosisas a basis for selective immunotherapy:from pipe dreams to (therapeutic)pipelines. Proc Natl Acad Sci USA 101:14599–14606

    Article  PubMed  CAS  Google Scholar 

  16. Kappos L, Radu EW, Antel J (2005)Promising results with a novel oralimmunomodulator-FTY720-in relapsingmultiple sclerosis. Mult Scler 11:S13

    Article  Google Scholar 

  17. Kleinschnitz C, Meuth SG, Kieseier BC,Wiendl H (2007) Immunotherapeuticapproaches in MS: update onpathophysiology and emerging agentsor strategies 2006. Endocr MetabImmune Disord Drug Targets 7:35–63

    CAS  Google Scholar 

  18. McFarland HF (2008) The B cell – oldplayer, new position on the team.N Engl J Med 358:664–665

    Article  PubMed  CAS  Google Scholar 

  19. Rice GP, Filippi M, Comi G (2000)Cladribine and progressive MS: clinicaland MRI outcomes of a multicentercontrolled trial. Cladribine MRI StudyGroup. Neurology 54:1145–1155

    PubMed  CAS  Google Scholar 

  20. Romine JS, Sipe JC, Koziol JA, Zyroff J,Beutler E (1999) A double-blind, placebo-controlled, randomized trial ofcladribine in relapsing-remittingmultiple sclerosis. Proc Association ofAmerican Physician 111:35–44

    Article  CAS  Google Scholar 

  21. Rose JW, Burns JB, Bjorklund J, Klein J,Watt HE, Carlson NG (2007) Daclizumabphase II trial in relapsing andremitting multiple sclerosis: MRI andclinical results. Neurology 69:785–789

    Article  PubMed  CAS  Google Scholar 

  22. Rose JW, Watt HE, White AT, CarlsonNG (2004) Treatment of multiple sclerosiswith an anti-interleukin-2 receptormonoclonal antibody. Ann Neurol56:864–867

    Article  PubMed  CAS  Google Scholar 

  23. Sakaguchi S (2005) Naturally arisingFoxp3-expressing CD25+CD4+ regulatoryT cells in immunological toleranceto self and non-self. Nat Immunol6:345–352

    Article  PubMed  CAS  Google Scholar 

  24. Sipe JC (2005) Cladribine for multiplesclerosis: review and current status.Expert Rev Neurother 5:721–727

    Article  PubMed  CAS  Google Scholar 

  25. Sipe JC, Romine JS, Koziol J, Zyroff J,McMillan R, Beutler E (1997) Cladribineimproves relapsing-remitting MS: adouble blind placebo controlled study.Neurology 48:A340

    Google Scholar 

  26. Sipe JC, Romine JS, Koziol JA,McMillan R, Zyroff J, Beutler E (1994)Cladribine in treatment of chronicprogressive multiple sclerosis [seecomments]. Lancet 344:9–13

    Article  PubMed  CAS  Google Scholar 

  27. Webb M, Tham CS, Lin FF, Lariosa-Willingham K, Yu N, Hale J, Mandala S,Chun J, Rao TS (2004) Sphingosine1-phosphate receptor agonists attenuaterelapsing-remitting experimentalautoimmune encephalitis in SJL mice.J Neuroimmunol 153:108–121

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Universität Würzburg, Klinik und Poliklinik für Neurologie, Josef-Schneider Str. 11, 97080, Würzburg, Germany

    Sven G. Meuth, Christoph Kleinschnitz & Heinz Wiendl

Authors
  1. Sven G. Meuth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christoph Kleinschnitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heinz Wiendl
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sven G. Meuth.

Additional information

Conflict of interest Sven G. Meuth received honoraria for lecturing and travel expenses for attending meetings from Bayer Healthcare/Bayer Vital and Merck Serono and serves as a consultant for Merck Serono. Heinz Wiendl has received honoraria for lecturing, travel expenses for attending meetings and financial support for research from Bayer Health Care, Biogen Idec, Merck Serono, Novartis, Sanofi Aventis, and TEVA. Christoph Kleinschnitz received honoraria for lecturing and travel expenses for attending meetings from Biogen Idec/Elan, Schering, Serono, Bayer and Sanofi Aventis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meuth, S.G., Kleinschnitz, C. & Wiendl, H. Recent clinical trials and future therapies. J Neurol 255 (Suppl 6), 93–96 (2008). https://doi.org/10.1007/s00415-008-6017-7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-008-6017-7

Key words

Search

Navigation