Fight SMA Annual Conference 2008
The Good Fight
Researchers' Conference
Families and Friends' Conference
- General Information
- Schedule of Events
- "Thriving with SMA" Panelists
- Nutrition Think Tank Panelists
- Capitol Hill Visits
Researchers' Conference
General Information
| When: | April 20-22, 2008 |
| Where: | L'Enfant Plaza Hotel 480 L'Enfant Plaza, SW Washington, D.C. |
Meeting Summary - By Dr. Chris Lorson, FightSMA's Science Director
 Chris Lorson, Ph.D. University of Missouri-Columbia |
Washington D.C was the host city once again for the annual FightSMA Research Conference, The Good Fight, was held April 21-22. Washington D.C. provides the ideal setting for this meeting as many of the SMA researchers are actively involved in pushing their local Representatives to support the SMA Treatment Acceleration Act, and the direct contact between SMA families and researchers provides a powerful one-two punch that truly delivers results on The Hill. Invited clinical and research specialists from around the world were in attendance to present and discuss their most recent unpublished data and to address several important, but unanswered questions in the SMA field. The following is a summary of the Research Conference.
Tremendous strides have been made since the identification of the SMA-determining gene regarding SMN function, however, it is still unclear why a defect in SMN results in the motor neuron disease. There are two primary concepts that have been proposed to explain the motor neuron-specific loss associated with SMN deficiencies. In the first scenario, SMN is involved in the generation of RNA/protein complexes required for proper gene expression, called snRNP (small nuclear ribonucleoproteins). Motor neurons have been proposed to have a uniquely high requirement for snRNPs that makes them especially sensitive to SMN levels. Additionally, analysis of the SMA mouse models has identified that a subset of snRNPs (referred to as the 'minor' pathway) are more perturbed in the SMA context than the snRNPs that are more likely to be involved in more general 'housekeeping' gene expression. For example, a computer-based analysis of the genes that are regulated by the 'minor' snRNP pathway are not randomly scattered throughout the genome, rather, a significantly large percentage of these genes encode factors that are likely involved in neuronal function, such as calcium channels. In the second scenario designed to explain the loss of motor neurons in SMA, SMN is predicted to be involved in the transport of RNA/protein complexes along the length of the axon toward the growth cone and the neuromuscular junction. SMN is associated with non-snRNP components, such as hnRNP proteins and beta-actin mRNA. To date, the primary focus has been upon snRNP biogenesis, however, this is an intriguing component of SMN function that still needs more attention. The recent discovery of plastin-3 as a potent SMA modifying gene by the Wirth laboratory indicates that axonogenesis is likely an important component of SMA development.
 Charlotte Sumner, M.D. Johns Hopkins University School of Medicine |
An addition to asking "what is the function of SMN," this meeting was designed to ask the question: what tissues require SMN expression? SMN expression was experimentally driven by relatively restrictive promoters, designed to express SMN exclusively in muscle or exclusively in neurons. Expression of SMN in neurons dramatically increased the life span of the severe SMA mice. In the severe SMA model, mice live ~3-5 days, whereas neuronal SMN expression extended the average life span to greater than 200 days. High levels of SMN expression in muscle did not significantly extend survival. These results are not to suggest that SMN does not perform an important function in SMA, but rather that SMN function in muscle is likely not directly linked to SMA development.
Building upon the molecular biology and biochemistry, several labs presented translational research programs designed to develop potential therapeutics for SMA. SMN protein is a very stable protein, however, the exon-skipped isoform is remarkable unstable and is rapidly degraded. Current work is being performed to better understand the regulation of SMN degradation as a means of increasing the intracellular pool of SMN.
Currently, a number of compounds are being examined in the SMA mouse model. Importantly, a detailed analysis of this mouse model has recently been published that identifies the most sensitive phenotypic traits that can be followed during drug testing. Several small molucules specifically target SMN and are designed to increase SMN expression, including tricostatin-A (TSA) and synthetic antisense oligonucleotides (AONs). Similar AONs have made tremendous strides in other genetic diseases, such as Duchenne muscular dystrophy. In the SMA context, AONs are used to increase full-length SMN expression from the SMN2 gene by modulating the pre-mRNA splicing regulatory factors. Modulating SMN2 gene expression at the RNA level through a variety of platforms is still extremely intriguing, however, the issue of delivery is a hurdle that faces SMA and other central nervous system disorders. Additional small molecule screens are being performed with optimized SMN reporters that are designed to identify the most robust SMN inducers. This novel platform has the potential to identify compounds that function through pathways such as transcriptional activation or SMN2 exon 7 splicing, but also through mechanisms that are more ambiguous, such as RNA stability or through minor contributions of multiple pathways.
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Reaction from an attending researcher: "This was an excellent selection of speakers from drug trials, basic biology, gene therapy and clinical studies. Overall, I thought the conference led to new understanding for all the covered topics and all attendees would walk away with excellent new information. I truly wouldn't change one thing." |
Gene therapy strategies were presented that included the development of vectors through a novel platform referred to as 'bio-panning' or in vitro evolution. In essence, a randomized pool of novel viral vectors can be generated and then through a series of enrichment steps using a mouse as 'bio-panning' tool, novel vectors can be identified that are ideally suited for specific gene expression in specific cellular lineages.
Collectively, this was an excellent forum to openly discuss cutting-edge research that continues to build the critical base of knowledge regarding SMN function, as well as the translational studies that are bringing novel compounds and molecules closer to clinical trial. FightSMA appreciates the hard work and dedication that the researchers bring each year to this meeting. Without your tireless efforts, SMA would not be at the exciting stage at which we now stand.
| 3:00 PM | Check-in for Researchers Opens | L'Enfant Plaza Hotel |
| 7:30 PM | Cocktail Reception | Renoir Room |
| 8:00 AM | Breakfast and Introduction by Dr. Chris Lorson | Renoir Room |
| 8:30 AM | SMN Function | |
| A genetic approach to the critical molecular pathway in spinal muscular atrophy using zebrafish and mice | Arthur Burghes | |
| SMN function in MN | Gary Bassell | |
| The role of SMN in the MN | Michael Sendtner | |
| 10:15 AM | Break | |
| 10:30 AM | SMN Function continued | |
| Consequences of SMN deficiency on snRNP biogenesis and function | Livio Pellizzoni | |
| SMN in muscle | Rashmi Kothary | |
| 12:30 PM | Lunch | Renoir Room |
| 1:30 PM | SMN translational research | |
| SMN stability and proteaosome inhibition | Barrington Burnett | |
| RNA mediated modulation of SMN2 pre-mRNA splicing | Chris Lorson | |
| SMN inducing signaling pathways | Alex MacKenzie | |
| 3:15 PM | Break | |
| 3:30 PM | SMN translational research continued | |
| Gene therapy applications in SMA | Nick Boulis | |
| Moving AAV from the bench to bedside for neuromuscular disorders | Brian Kaspar | |
| Development of Therapeutics for SMA | Matthew Butchbach | |
| 5:30 PM | Break | |
| 7:00 PM | Dinner | Degas Room |
| 8:00 AM | Breakfast | Renoir Room |
| 8:30 AM | SMN translational research continued | |
| Identification of new SMN inducing compounds | Elliot Androphy | |
| SMN anti-sense | Adrian Krainer | |
| HDAC inhibitors in mice | Charlotte Sumner | |
| 10:15 AM | Break | |
| 10:30 AM | SMN translational research continued | |
| Discovery Initiatives and Research Priorities | Meg Winberg | |
| 11:45 AM | Clinical Trials Update | Kathy Swoboda |
| 12:30 PM | Lunch | Renoir Room |
| Conclusion | Chris Lorson | |
| Elliot Androphy, M.D. | University of Massachusetts Medical School |
| Gary Bassell, Ph.D. | Emory University School of Medicine |
| Nicholas Boulis, M.D. | Emory University School of Medicine |
| Arthur Burghes, Ph.D. | Ohio State University |
| Barrington Burnett, Ph.D | National Institutes of Health |
| Matthew Butchbach, Ph.D. | Ohio State University |
| Kenneth Fischbeck, M.D. | National Institute of Neurological Disorders and Stroke |
| Katrina Gwinn-Hardy, M.D. | National Institutes of Health |
| Brian K. Kaspar, Ph.D. | The Research Institute at Nationwide Children's Hospital |
| Rashmi Kothary, Ph. D. | Ottawa Health Research Institute |
| Adrian Krainer, Ph.D. | Cold Spring Harbor Laboratory |
| Robert Leshner, M.D. | Children's National Medical Center |
| Chris Lorson, Ph.D. | University of Missouri-Columbia |
| Alex MacKenzie, M.D., Ph.D. | Children's Hospital of Eastern Ontario Research Institute |
| Marco Passini, Ph.D. | Genzyme Corporation |
| Livio Pellizzoni, Ph.D. | Columbia University Center for Motor Neuron Biology and Disease |
| Michael Sendtner, M.D. | University of Wurzburg |
| Charlotte Sumner, M.D. | Johns Hopkins University School of Medicine |
| Kathy Swoboda, M.D. | University of Utah |
| Meg Winberg, Ph.D. | Spinal Muscular Atrophy Foundation |
Families and Friends' Conference
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What was the aspect of the FightSMA Annual Conference that most influenced your decision to attend? "To network with other moms and having my daughter network with other children that are going through what she is, for her not to feel alone. And this is the one time a year that [she] can be around a group of kids and know that they have what she has." |
General Information
| When: | April 22-25, 2008 |
| Where: | L'Enfant Plaza Hotel 480 L'Enfant Plaza, SW Washington, D.C. |
| 3:00 PM | Check-in for Families and Friends Opens | L'Enfant Plaza Hotel |
| 7:00 PM | Reception and Check-In | Monet 3 Room |
| 8:30 AM | Check-In | Outside Monet 1 Room |
| 9:00 AM | Breakfast | Monet 1 and 2 Rooms |
| 9:15 AM | Science Update | Dr. Chris Lorson Dr. Alex MacKenzie |
| 9:45 AM | Break | |
| 10:00 AM | Thriving with SMA Panel | |
| 12:00 PM | Lunch | Monet 1 and 2 Rooms |
| 1:00 PM | Nutrition Panel | |
| 3:00 PM | Break | |
| 3:30 PM | One-on-one Meetings | Monet 1 and 2 Rooms |
| 5:30 PM | Break | |
| 7:00 PM | Dinner | Monet 1 and 2 Rooms |
| 7:30 AM | Breakfast and Capitol Hill Briefing | Monet 1 and 2 Rooms |
| 9:00 AM | Visits to Capitol Hill Representatives | |
 Dr. Joan Gold meets with the Robbins family |
Joan Gold, M.D. - Rusk Institute of Rehabilitation Medicine
Dr. Gold is Clinical Director of Children's Rehabilitation Services at the Rusk Institute of Rehabilitation Medicine at the New York University School of Medicine. She has a medical specialty in pediatric rehabilitation, with a special interest in disabling and developmental disorders of childhood.
Petra Kaufmann, M.D., M.Sc - Columbia University
Dr. Kaufmann is a neurologist specializing in neuromuscular diseases and clinical trials. She is a member of the Neuromuscular Division in the Columbia University Department of Neurology and she is co-director of the SMA Clinical Research Center. Dr. Kaufmann is active in several investigator groups for neuromuscular disease, including the International Coordinating Committee for SMA (ICC) for which she co-chairs the Trial Design Group.
Robert Leshner, M.D. - Children's National Medical Center
Dr. Leshner is a professor of pediatrics and a senior staff neurologist at Children's National Medical Center (CNMC) in Washington, D.C. He acts as Medical Director for Cooperative International Neuromuscular Research Group and Co-Director of the Wellstone Muscular Dystrophy Center. In 2004, Dr. Leshner relocated to Washington D.C. to assist in the development of clinical neuromuscular programs and the facilitation of translational research in Muscular Dystrophy and Spinal Muscular Atrophy at the CNMC and the Center for Genetic Medicine. Dr. Leshner will serve as the moderator for the Thriving with SMA panel.
 Dr. Stephen Smith meets with Ann and Elliot Eisenberg |
Stephen Smith, M.D. - Gillette Children's Specialty Healthcare
Dr. Smith is a pediatric neurologist at Gillette Children's Specialty Healthcare in St. Paul, Minnesota with more than 30 years experience treating pediatric neuromuscular disease. He sees patients with muscular dystrophy, spinal muscular atrophy, and other neuromuscular conditions and has a special interest in neuromuscular pathology. Dr. Smith has lectured on neuromuscular disease, has conducted SMA studies, and is an investigator for AmSMArt, the American Spinal Muscular Atrophy Randomized Trials.
Kathy Swoboda, M.D. - University of Utah
Dr. Swoboda is an associate professor of Neurology and Pediatrics at the University of Utah, where she directs the Pediatric Motor Disorders Research Program and Neuromuscular Electrodiagnostic Laboratory at Primary Children's Medical Center in Salt Lake City. She is the principal investigator for the Project Cure SMA Investigator's Network, an international multi-center clinical research collaboration intended to facilitate the rapid translation of new therapies for treatment trials. She has conducted and is conducting multiple clinical trials, including studies into metabolic dysfunction in SMA patients and the effects of Valproic Acid, Sodium Phenylbutyrate, and Carnitine.
 Clinical Specialist Brian Weaver, Dr. Petra Kaufmann, and Dr. Ching Wang join the "Thriving with SMA" panel |
Ching Wang, M.D., Ph.D. - Stanford University Medical Center
Dr. Wang is Director of the Pediatric Neuromuscular Clinic at Lucile Packard Children's Hospital and the primary investigator for the SMA Research Group at Stanford University Medical Center. He was a driving force behind the organization of and publication of the recent Consensus Statement for Standard of Care in Spinal Muscular Atrophy.
Brian Weaver, M.S., RRT-NPS, RPFT - University of Medicine & Dentistry of New Jersey
Mr. Weaver is the Clinical Specialist for Respiratory Therapy and part of the administration staff at The University Hospital / University of Medicine & Dentistry of New Jersey. He specializes in Perinatal/Pediatric respiratory care. He is published and has lectured on respiratory therapy for neuromuscular impaired patients including, Type I and Type II SMA. Mr. Weaver has taught families and healthcare personnel both nationally and internationally about respiratory problems, airway clearance techniques, equipment, and protocols, including noninvasive ventilation alternatives.
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Reaction from an attending family member: "I would highly suggest extended family members try to attend this confrence. I think over the years we sometimes become very complacent. The families of these children live such graceful and courageous lives. It becomes their normal. They truly impose nothing on the rest of us. Most of the time we know nothing of their daily burden and heartbreak. We all show up for the yearly fundraiser and think we know about this disease and have done our part. Not so..." |
Nutrition Think Tank Panelists
Petra Kaufmann, M.D., M.Sc - Columbia University
Dr. Kaufmann is a neurologist specializing in neuromuscular diseases and clinical trials. She is a member of the Neuromuscular Division in the Columbia University Department of Neurology and she is co-director of the SMA Clinical Research Center. Dr. Kaufmann is active in several investigator groups for neuromuscular disease, including the International Coordinating Committee for SMA (ICC) for which she co-chairs the Trial Design Group.
Nancy Kuntz, M.D. - Mayo Clinic
Dr. Kuntz is board certified in neurology and pediatrics. She practices at the Mayo Clinic in Rochester, Minnesota and is an investigator for AmSMArt, the American Spinal Muscular Atrophy Randomized Trials.
Alex MacKenzie, M.D., Ph.D. - Children's Hospital of Eastern Ontario Research Institute
Dr. MacKenzie is a professor in the Department of Pediatrics and Biochemistry at the University of Ottawa, in addition to being the Director of the Children's Hospital of Eastern Ontario Research Institute and the Vice President of Research at the Children's Hospital of Eastern Ontario. Dr. MacKenzie will serve as the moderator for the nutrition panel.
Charlotte Sumner, M.D. - Johns Hopkins University School of Medicine
After completing a neuromuscular fellowship at The Johns Hopkins University and a neurogenetics fellowship in the Neurogenetics Branch at the National Institute of Neurological Disorders and Stroke, Dr. Sumner joined the neurology faculty at Johns Hopkins School of Medicine in 2006.
 Drs. Kathy Swoboda, Nancy Kuntz, Petra Kaufmann, and Charlotte Sumner discuss nutrition and SMA |
Kathy Swoboda, M.D. - University of Utah
Dr. Swoboda is an associate professor of Neurology and Pediatrics at the University of Utah, where she directs the Pediatric Motor Disorders Research Program and Neuromuscular Electrodiagnostic Laboratory at Primary Children's Medical Center in Salt Lake City. She is the principal investigator for the Project Cure SMA Investigator's Network, an international multi-center clinical research collaboration intended to facilitate the rapid translation of new therapies for treatment trials. She has conducted and is conducting multiple clinical trials, including studies into metabolic dysfunction in SMA patients and the effects of Valproic Acid, Sodium Phenylbutyrate, and Carnitine.
On April 26, 2008, attendees of the FightSMA Annual Conference once again marched upon Capitol Hill to champion their cause - to find a cure or treatment for Spinal Muscular Atrophy. Attendees from 19 states visited in over 70 Congressional offices to show their support of the SMA Treatment Acceleration Act (H.R. 3334, S. 2042).
 Trevor Smith meets with Rep. C. W. Bill Young (FL-R) |
Families and friends of the SMA community have been aggressively advocating for the support and passage of the SMA Treatment Acceleration Act. As a direct result, this important legislation now boasts 52 Cosponsors in the House and 15 in the Senate (as of June 11, 2008 - updated list available by clicking here).
We will continue to fight "The Good Fight" until this paramount legislation - the first SMA bill in history - is law.
For more information on the bill and how to reach out to your Members of Congress, please contact Caroline Gibson.
Conference Sponsors
The 2008 FightSMA Annual Conference: The Good Fight is sponsored in part by the
National Institute of Neurological Disorders and Stroke (NIH) and the Office of Rare Diseases (NIH).
FightSMA would like to thank the following businesses for their generous support of the
2008 FightSMA Annual Conference: The Good Fight.
A special thank you to SMA Angels Charity for their friendship, generosity, and support.
SMA Angels Charity