Regeneration Research NEWSLETTER The Twelfth International Symposium on Neural Regeneration The Twelfth International Symposium on Discoveries/University of British Columbia). Neural Regeneration (ISNR) was held at the Guest attendees representing co-sponsoring Asilomar Conference Center in Pacific Grove, institutions at the planning meeting were Drs. California from December 5-9, 2007. The meet- Vivian Beyda (United Spinal Association) and ing was co-sponsored by the U.S. Department of Naomi Kleitman (NIH-NINDS). Veterans Affairs (Biological Laboratory Research The keynote speaker for this year’s sym- and Development and Rehabilitation Research posium was Stephen Waxman from Yale Medical and Development Service), the Paralyzed School. Featured talks were given by Melitta Veterans of America (Spinal Cord Research Schachner from Universitat Hamburg and Foundation), the National Institutes of Health Rutgers University, Douglas Kerr from Johns (National Institute of Neurological Disorders and Hopkins University School of Medicine, Steven Stroke, and Office of Rare Diseases), the Cramer from the University of California - Irvine, Christopher and Dana Reeve Foundation and Douglas Wallace from the University of California the United Spinal Association. Additionally, a - Irvine and Michael Fehlings from the University generous donation was received from the of Toronto. Shapiro Spinal Cord Research Foundation. The Symposium was organized by Dr. Roger Madison (Symposium Director, VA ISNR Staff Medical Center and Duke University, Durham, Director: Roger Madison, Ph.D. NC), and the program planning committee which included Drs. David Gardiner (University of Layout and Design: Frances Stuart California, Irvine), Jane Lebkowski (Geron Photo Credits: Rao Chadaram Corporation), Michael Sofroniew (University of California, Los Angeles) and John Steeves (International Collaboration on Repair Continued, page 3 OFFICE OF THE INTERNATIONAL SYMPOSIUM ON NEURAL REGENERATION June 2008 The Director’s Chair From the Office of the International Symposium on Neural Regeneration Roger D. Madison, Ph.D. - Director 2007 Highlights The International Symposium on Neural Regeneration celebrated another successful gathering at the 2007 conference which was attended by 216 participants, including 66 students, with a total of 91 posters being presented. All of the symposium events were of great interest to the participants with the debate and trainee awards drawing the most interest. The debate session of the symposium was another successful event. The focus was “Growth Across the Glial Scar Will Be Sufficient for Functional Recovery” and was again chaired by Keith Crutcher (University of Cincinnati). James Fawcett (University of Cambridge), Paul Reier (University of Florida) and Jerry Silver (Case Western Reserve University) along with Jeffery Kocsis (Yale University), Edward Hall (University of Kentucky) and Oswald Steward (University of California - Irvine) participated. The debate session had the highest attendance of any session at the symposium. The format included a group presentation of each side’s argument fol- lowed by a rebuttal period. The debate sparked much con- versation throughout the remainder of the symposium. (Pictured at left are members of the 2007 ISNR Debate Teams - L to R are James Fawcett, Paul Reier, Jerry Silver, Keith Crutcher, Jeff Kocsis, Ed Hall and Os Steward) The Fredrick Seil Trainee Award, which was established in 2003 to honor the first director and founder of ISNR, was awarded for 2007 to Angela Scott and Lesley Soril, both representing the University of British Columbia and International Collaboration on Repair Discoveries (ICORD). Each received a $250 cash award, and their names have been engraved on the Frederick Seil Trainee Award perpetual plaque. As an added bonus, Dr. Seil was in attendance at the meeting and personally presented the awards. Additional poster awards were presented by Dr. Vivian Beyda of the United Spinal Association to recognize Ward Plunet (UBC/ICORD), Jacquelyn Cragg (UBC/ICORD), Qin Chen (Baylor), Joe Bonner (Drexel University) and Jennifer Wong (UBC/ICORD). The United Spinal Association generously provided a $50 cash award and a certifi- Lesley Soril and Angela Scott cate for each of these winners. All awards were chosen by planning board members who reviewed the poster sessions. In addition to these poster awards, two individuals were selected to give platform presentations based on the abstracts they submitted. Michael Shifman of the University of Pennsylvania and Allan Bieber of the Mayo Clinic were chosen to give these talks in the final “Emerging Topics” confer- ence session. ISNR congratulates all of these winners. 2 OFFICE OF THE INTERNATIONAL SYMPOSIUM ON NEURAL REGENERATION June 2008 Continued from page 1 axons, and thus may provide a molecular sub- strate for clinical remissions in disorders such as Following the format of preceding neural multiple sclerosis (MS). Dr. Waxman concluded regeneration symposia, the grogram was divided by discussing the complexity of the path from lab- into six sessions, which included: 1) Intrinsic oratory bench to clinic. Mechanisms of Regeneration, chaired by Herbert Geller; 2) MR Imaging of Spinal Cord Injury and Recognition Molecules and Neural Repair Repair, chaired by Patrick Stroman; 3) Role of (Melitta Schachner, Universitat Training, Synaptic Plasticity and Learning on Hamburg/Rutgers University) Functional Recovery, chaired by Fernando Dr. Schachner's presenta- Gomez-Pinilla; 4) Growth Across the Glial Scar tion included recent work Will Be Sufficient for Functional Recovery highlighting both the benefi- (debate), chaired by Keith Crutcher; 5) Human cial and adverse impacts of Stem Cells for Model Development and Repair: immunoglobulin superfamily Opportunities and Challenges, chaired by Arlene adhesion molecules and Chiu; and 6) Emerging Topics/Clinical Updates, extracellular matrix glycopro- chaired by Naomi Kleitman. Brief summaries of teins on regeneration after spinal cord injury in the keynote and featured speakers presentations the adult mouse. Overexpression of the are given below followed by a listing of session immunoglobulin superfamily adhesion molecule chairmen and speakers. L1 by embryonic stem cells or application of adeno-associated virus encoding for L1 promot- Men on Wheels, Men on Fire: Sodium ed functional recovery, while CHL1 was adver- Channels as Molecular Targets in Disorders sive to regeneration. Adhesion molecule-associ- of the Spinal Cord (Stephen Waxman, Yale ated carbohydrates, such as the human natural Medical School) killer cell antigen 1 (HNK-1) and the neural cell Dr. Waxman began his adhesion molecule NCAM associated polysialic keynote address by stating acid enhanced regeneration in the central and that voltage-gated sodium peripheral nervous system of adult mice. Dr. channels are widely Schachner concluded by stressing that combina- expressed within neurons and torial approaches in targeting will be important for play pivotal roles in neuronal future therapy. signaling. Although neuro- physiology classically referred to "the" sodium Stem Cells and Spinal Cord Disorders: channel as if it were a singular entity, it is now Models of Disease and Therapeutic known that ten different genes encode ten differ- Strategies (Douglas Kerr, Johns Hopkins ent isoforms of sodium channels, with different University School of Medicine) kinetic and voltage-dependent properties. It is Dr. Kerr's presentation thus not surprising that sodium channels can reviewed recent work with sev- play multiple roles in neuronal pathophysiology. eral stem cell-based therapies Dr. Waxman described the human hereditary for multiple sclerosis (MS), trans- pain disorder (erythromelalgia, the "man on fire verse myelitis (TM) and spinal syndrome") which is due to a gain-of-function muscular atrophy (SMA). He mutation in a sodium channel that makes noci- presented promising data ceptive DRG neurons hyperexcitable, thus pro- using high-dose cyclophos- viding a model in humans of chronic pain due to phamide (Revimmune) as a one-time front- sodium channel dysfunction. Conversely, loaded therapy to induce long term remission in changes in the expression of sodium channels patients with can play an adaptive role in some demyelinated MS. In preliminary work with 10 patients there OFFICE OF THE INTERNATIONAL SYMPOSIUM ON NEURAL REGENERATION June 2008 3 was a 90% reduction in gadolinium enhancement tions have been linked to a wide range of meta- by 18 months, a 95% reduction in exacerbation bolic and degenerative diseases, and somatic frequency and a 45% reduction in disability. Dr. mtDNA mutations accumulate with age in a Kerr also reported on preclinical studies using broad spectrum of organisms. Introduction of glial restricted precursors (GRPs) as potential catalase into the mouse mitochondrial matrix therapeutic agents for CNS demyelinating disor- reduces the mtDNA somatic mutation rate and ders, with the goal of initiating a single center, extends life span, and treating short-lived open label pilot study with dose escalation to Drosophila mutants with mitochondrially-targeted obtain preliminary data on the safety and tolera- antioxidants can restore the life span. Ancient bility of GRP cells in patients with disability from adaptive mtDNA polymorphisms have been TM. He closed with reviewing the ability of associated with altered risk for metabolic and embryonic stem cell-derived motor neurons to neurodegenerative diseases, such as metabolic functionally