neuroimmunotherapeutics comes of age

EDITORIAL

Neuroimmunotherapeutics Comes of Age

This issue of Neurotherapeutics addresses immunetherapies for neurological disease. Much of the issue isfocused on multiple sclerosis (MS), which is the mostimportant immunologically-mediated neurologicaldisorder from the standpoint of number affected andburden of morbidity. Furthermore, MS has been theobject of increasingly intense research scrutiny duringrecent decades. However, an attempt has been made toexpand the field of view to encompass other disorders,often bringing to bear insights into neuroimmunologyand therapeutic intervention in neuroinflammation, de-rived from MS research.We have been fortunate to recruit authentic expert

clinician/scientists as contributors to this issue. Eachcontribution was prepared by a leading investigator withan active research program in the topic of discussion.This issue is organized into three sections, which is de-scribed as follows.In the first section, we assembled current reviews of

some of the major players in the inflammatory pro-cesses of the nervous system, while maintaining anemphasis on the therapeutic implications of suchknowledge. Monica Carson and colleagues wroteabout microglia (pages 571–579), the intrinsic inflam-matory and immune cells of the CNS. V. Wee Yongand coworkers discussed the matrix metalloproteinases(pages 580–589). In addition, Carine Savarin-Vuaillatand Richard Ransohoff described the chemokine andchemokine receptor system (pages 590–601). All to-gether, these reviews address the intrinsic inflamma-tory and immune cells of the CNS (microglia), animportant effector and modulatory system (MMPs),and the apparatus for recruiting and activating leuko-cytes from the bloodstream (chemokines). Rohit Bak-shi and colleagues (pages 602–617) provided an in-depth discussion of magnetic resonance imaging,which constitutes a critical means for applying anytherapeutic initiatives for MS.In the second section, current therapies for MS are

discussed. Elliot Frohman and coworkers (pages 618–626 and 627–632) discussed the application of cortico-steroids, a drug class often used, but too little discussed.Frohman and coworkers addressed both the use of theseagents in MS attacks and the novel concept that disease-modifying effects can be mediated by corticosteroids ina fashion that maintains acceptable risk–benefit ratios.Richard Rudick and Rob Bermel (pages 633–646) com-

prehensively reviewed interferon-beta treatment for MS,tackling the most widely used, yet still poorly understoodagent for this disease. Martin Weber, Reinhard Hohlfeld,and Scott Zamvil discussed glatiramer acetate, consider-ing its decades-long history and describing research asrecently published as Summer, 2007 (pages 647–653).Peter Hartung and colleagues (pages 654–660) providedan overview of the immunosuppressants that form themainstay of second-stage therapy for the large fraction ofour patients for whom the first-line agents do not ade-quately control the disease.The third section looks toward the future. This sec-

tion begins with Larry Steinman’s essay on the desiredendpoint of all MS research (pages 661–665) (i.e., atherapy that eliminates the pathogenic autoreactivitywithout immunosuppression). Samia Khoury and Vis-sia Viglietta (pages 666–675) described how the re-quirement of the T cell for co-stimulation by the an-tigen-presenting cell at the time of antigen recognitionmight be used to modify or inhibit pathogenic auto-immunity in MS. Paolo Muraro and Bibi Bielekovagave a wide range and scholarly series of commentsregarding varied new approaches to MS therapy(pages 676–692), all of which could potentially reachfull-scale clinical application; however, not all ofthese approaches will be achieved to reach this end-point. Martin Weber, Larry Steinman, and Scott Zam-vil gave an in-depth treatment of the means by whichthe statins (i.e., drugs that have changed the face ofatherosclerosis management) may also impact in-flammatory and neurodegenerative disease (pages693–700). The current volume concludes with reviewsconcerning two highly exciting topics. Jaime Imitolainstructs us on the prospects for the use of stem cellsor progenitor cells for therapeutics (pages 701–714),which includes a full recognition of the need to un-derstand both the disease under consideration and thebiology of the cell being applied for its amelioration.Pedro Lowenstein, Kurt Kroger, and Maria Castroconclude this issue of the journal with their presenta-tion of the remarkable promise of gene therapy usingviral vectors (pages 715–724), and they remind us thatthe immune and inflammatory reaction of the host tosuch interventions must be acknowledged and under-stood.Throughout, we have tried to provide important in-

formation that we believe to be authoritative, timely,

Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics

Vol. 4, 569–570, October 2007 © The American Society for Experimental NeuroTherapeutics, Inc. 569

and practical, if only in the sense of responding topatient questions about what is on the horizon. Thevolume is not comprehensive, due to space limitations.What is missing? We were not able to include theperipheral nervous system immune/inflammatory dis-orders or their treatments such as intravenous immu-noglobulin. We did not discuss plasma exchange as atreatment for CNS and peripheral nervous system dis-orders. We regret these and other omissions occa-sioned by the space available for this volume. It is ourhope that the material presented here will be helpful for thereaders of this journal, and that it gives a full measure ofrecognition both for the distance traveled in the conduct ofthis research and for the miles left to go.

Richard M. Ransohoff, MDDepartment of Neurosciences

Neuroinflammation Research CenterLerner Research Institute and

Mellen Center for MS Treatment and ResearchCleveland Clinic Foundation

9500 Euclid AvenueCleveland, OH 44195

Scott S. Zamvil, MD, PhDDepartment of Neurology and Program in Immunology

University of California, San Francisco513 Parnassus Avenue

Rm. S-268San Francisco, CA 94143

RANSOHOFF AND ZAMVIL570

Neurotherapeutics, Vol. 4, No. 4, 2007