Fight SMA Annual Conference 2006
The Good Fight
FightSMA Annual Meeting
April 23-28, 2006
Melrose Hotel, Washington, D.C.
• Report from Annual FightSMA Meeting
• Thriving with SMA Panel
• Summary of Science Presentations
• 4th Annual SMA Coalition Day on Capitol Hill
• Additional Information about the Meeting
More than 50 representatives of the FightSMA community gathered in Washington April 23 – 28, 2006 to learn about the latest developments in research and treatment and to meet with their national representatives to press the need for more federal support for SMA research.
In conjunction with this meeting, some two dozen researchers met to share information and
ideas on basic and clinical work being done on SMA and other motor neuron diseases and to discuss the latest developments in stem cell research.
This is the tenth year FightSMA has organized an annual meeting for researchers and families and the fourth year that the families have met with Members of Congress and Senators in Washington.
This year’s conference, “The Good Fight,” was longer than previous meetings with two full days devoted to meetings for researchers and two more days during which time families had a chance to learn about new developments in research. A panel discussion featuring presentations from
doctors – pulmonologists and neurologists, as well as a psychotherapist, speech pathologist, occupational therapist, and respiratory therapist—looked at treatment methods to help SMA patients thrive. A second day for families was devoted to meetings on Capitol Hill.
While “The Good Fight” added new elements to the SMA annual meeting, it was designed
with FightSMA’s mission in mind:
To strategically accelerate research toward treatment and a cure for spinal muscular atrophy, a deadly crippler and the number-one inherited genetic cause of infant death.
In planning the meeting, FightSMA Scientific Advisory Committee Co-Chairs, Dr. Chris Lorson, from the
University of Missouri-Columbia, and Dr. Alex MacKenzie, from Children’s Hospital of Eastern
Ontario, worked together to identify researchers for the conference on Monday and Tuesday, as well as
the “Thriving with SMA” panel discussion on Wednesday.
FightSMA President Martha Slay also proposed that the SMA researchers meet with doctors working on ALS and stem cells. Dr. Lorson said doctors working on ALS, another neurodegenerative disorder, are “on a similar path” as SMA researchers. Dr. Jean-Pierre Julien of Laval University in Quebec, Dr. Jonathan Glass of Emory University School of Medicine and Dr. Jeffrey Rothstein of Johns Hopkins University shared information on their studies, leading to exciting discussions between these world-leading scientists.
Dr. Doug Kerr is a member of the FightSMA Scientific Advisory Council and has been working with the SMA community for several years. Dr. Kerr discussed his pioneer work on stem cells and the significant progress made in the last year. Drs. Clive Svenden of the University of Wisconsin and Hans Keirstead of the University of California-Irvine shared information on understanding stem cell biology, the developing pure motor neuron cultures from stem cells and possible stem cell therapies. Dr. Lorson says SMA is ideally suited for this type of therapy and identified Keirstead as a pioneer who is taking the use of stem cells from a scientific endeavor to a real-world product.
Dr. Chris Lorson reviewed the first two days of the meeting with SMA families Wednesday morning. He and Dr. MacKenzie discussed work being done on SMA mouse models, HDAC inhibitors, clinical trials, and the search through data banks that could yield useful information on SMA and work on stem cells.
Dr. Robert Leshner from Children’s National Medical Center in Washington, D.C., opened the panel on “Thriving with SMA” telling parents that the natural history of SMA is being rewritten everyday–both in the labs where researchers are working and in homes where SMA families come up with new strategies to deal with their children’s needs.
“You should demand from doctors that they listen and learn from you,” Leshner told them.
He encouraged them to use their doctors as advocates in schools and with vocational services to make sure their children get the care they need.
Doctors, he said can also help them sort out information.“We can help you distinguish
what’s promising, what’s valid, and what’s bogus,” he said.“We can protect you from medical con artists.”
Most of all, he said, doctors should be available and accessible, and parents have the right
to demand that for their children.
Presenters included pediatric pulmonologists Dr. Mary Schroth, Dr. Sherri Katz, and Dr.
Chris Makris, pediatric neurologist Kathy Swoboda, and physiatrist Dr. John Bach, who has
written books on The Management of Patients with Neuromuscular Diseases and
Noninvasive Mechanical Ventilation.
Pyschoanalytic psychotherapist Dr. Eleanore Rothenberg, occupation therapist Dr. Jennifer Hewitt, speech language pathologist Jennifer Barnes, and respiratory therapist Brian Weaver also shared their insights on treating children with SMA as well as members of their families.
After the formal panel discussions, parents had an opportunity to meet individually with the
doctors and therapists who sat at tables throughout the room.
Dr. Lorson said this intimate setting and the time to sit and talk with families helps put his work in the lab in perspective. For Holly and John Bolton, from Charlotte, North Carolina, the conference was a great opportunity to talk with other parents and learn more about treatment and research.
Thursday was reserved for congressional visits. After a presentation by Donna Mullins and Laura Breiteneicher from the public affairs group Winning Strategies, SMA families traveled to Capitol Hill for 60 meetings with Senators, U.S. Representatives, and their staff that had been set up ahead of time.
After four days of meetings and talks, parents and other SMA family members left Washington with FightSMA t-shirts, hats, and magnets, and a renewed sense of purpose and hope for the children.
“Our meetings were very energizing. We vow to come back next year to the Hill to visit again!” – Melissa Andrade, Waysata, Minnesota.
The Wednesday morning panel discussion during the FightSMA annual meeting in Washington gave attendees an opportunity to hear the latest thinking on treatment. The panel included some of the leading pediatric pulmonologists and neurologists working with SMA patients as well as other doctors and therapists who are part of the health care team.
Dr. Robert Leshner, a professor of neurology and pediatrics at Children’s National Medical
Center in Washington D.C., moderated the panel.
He urged SMA families to push for a dialogue with their doctors and other health care providers so there is an open and free exchange of information.“Hopefully, you’ll get a mini-course every time you visit your clinic, and your care givers will get a mini-course from you.
Jennifer Barnes, a speech language pathologist from Children’s Healthcare of Atlanta, discussed the role of speech therapy for children with SMA.
“We look at breathing, eating and speaking–we deal with respiratory issues first.”
And, while children with SMA can have language problems, Barnes says these same children have also been shown to have precocious language skills, which helps them follow complex directions they are often given for their care.
Barnes said she tries to maximize treatment by teaching parents techniques to help their children,
then backs off and monitors what the parents are doing until the child’s needs change. Then
she teaches new techniques.
Dr. Eli Rothenberg, a psychotherapist, who runs The Sibling Center in New York, discussed her work helping children cope with the special stresses that come with being the brother or sister of a child with a severe disorder.
“These siblings have feelings of sadness, anger and guilt,” she said.“Because most of the family’s resources–both time and money–go to the child with the disability, the sibling can suffer from a loss of self esteem.”
At her clinic, these brothers and sisters have a place to share their feelings with other
children who have the same experiences and learn ways to cope with their feelings. At the
center, “the children learn that it’s okay to feel sad, but also okay to have fun and be
For more information on Dr. Rothenberg’s work and the Sibling Center, see the winter
update on the Fighter Mom section of the FightSMA Web site.
Pediatric pulmonologists Mary Schroth from the University of Wisconsin and Chris Makris of Children’s Hospital in Birmingham, Alabama, talked about methods to help children breathe.
Schroth and Makris both advocate use of the cough assist machine or in-exsufflator to help children get
rid of secretions when they aren’t able to cough on their own.Schroth also recommends use of a BI-
PAP during the night for children with Type 1 SMA. Makris said that besides the cough assist machine,
an oximeter used to monitor sleep will also make sure the child is getting enough oxygen at night.
Neither Schroth or Makris recommended tracheotomies, but Makris said it’s important to discuss options with your doctor early on.
“Where you go is a family decision,” he said, “and both parents have to be at peace with that decision.”
Parents may have to educate doctors about the latest developments in care and–in some
cases–take machines they have at home to emergency rooms and hospitals.
Dr. John Bach, a physiatrist from the University of Medicine and Dentistry of New Jersey expanded on this discussion. Bach, Makris noted, has been a pioneer in pushing non-invasive methods to help SMA patients breathe.
Bach advocates the use of oximeters to measure xygen and respiration, BI-PAPs, and cough assist machines.
“Almost 90 percent of mortality in Type 1 SMA patients is caused by colds that have developed
into pneumonia,” Bach said. “The cough assist is the most important aid you can have to avoid
He also pointed to a study that showed children who used his method had dramatically lower rates of hospitalization.
Brian Weaver, a respiratory therapist, who works with Dr. Bach, talked about his work educating doctors and other respiratory therapists.
“I’m fighting the good fight for you,” Weaver told the group.He has phoned and visited ICUs and ERs at other hospitals to explain how to use noninvasive ventilation methods. He urged parents to review protocol with doctors and refer them to Dr. Bach’s website and books to help explain what their child needs. “It’s all about being really aggressive,” he said. Dr. Sherri Katz, a respirologist at the Children’s Hospital of Eastern Ontario, promoted the
use of BI-PAP therapy at night.She recommended giving the mask to the child to play with
during the day to experiment with.It’s important for the child to be comfortable with the
mask, so they wear it.
Jennifer Hewitt, an occupational therapist at Children’s Healthcare of Atlanta, said each child needs to be evaluated for their individual needs.“Focus on goals,” she said.“Goals should be reasonable, functional, achievable, and measurable.”
Part of her job is to recommend adaptive equipment to help the child function at school and at play.This equipment can be as simple as a pair of scissors to help at school or a bike. “No matter what level your child is at,” she said. “There is equipment to help.”
There are also exercise such as yoga, aquatic programs, and horseback riding that–with the proper training and equipment– can help the child with SMA. Dr. Hewitt is certified in Yoga for the Special Child and advocates its use to help children with breathing, posture, and flexibility.
Dr. Kathy Swoboda, a pediatric neurologist at the University of Utah who is working on Project Cure, discussed the special nutritional needs of children with SMA. She has been testing Valproic acid to increase protein production.
SMA children especially need to follow guidelines on nutrition, calories, and percentage of fat in their diets since their energy needs are lower:“Getting rid of processed foods will help reduce constipation and reflux,” she said.
With so many health care professionals involved in the treatment of a child with SMA, communication is very important.
Speech therapist Jennifer Barnes offered parents this advice:
Pick a team you can communicate with, and make sure team members communicate and
coordinate with other team members. Pick a team that cares for your child–they need to
treat the whole child.”
Anneliese Schaefer (PhD, Washington University): Dr. Schaefer focuses upon
understanding the mechanisms of motor neuron degeneration by using high resolution
imaging of axons and neuromuscular junctions in mouse models of SMA. This is made
possible by using SMA mice that have an additional transgene (a genetically introduced
gene) called YFP that illuminates specific sets of neurons. Relatively little is known about how neurons live and die during the development of SMA and this work will provide
important information about the fate of neurons within an organismal context. Elliot Androphy (MD, University of Massachusetts): Dr. Androphy has played in
important role in the drug-discovery process in SMA by developing “reporter genes” for
SMN2 induction. To screen large numbers of compounds (100,000 – 1,000,000+), it is not
practical to look at SMN protein levels or SMN splicing levels. Therefore, these “reporter
genes” are smaller replicas on the SMN2 gene, but an additional molecule (e.g. that
fluoresces) is attached to the SMN2 gene that makes the analysis relatively simple and
more amenable to large scale analysis. Dr. Androphy’s lab has recently developed a new
SMN2 reporter gene that is designed to more closely mimic the normal SMN2 gene found in
patients. This is important because it may identify new classes of SMN2-inducing
compounds are lead to the development of more specific SMN2-inducing compounds.
Christian Lorson (PhD, University of Missouri): Dr. Lorson is interested in
understanding how the SMN2-encoded protein functions. SMN2 primarily makes a shortened
protein that is very unstable and cannot perform all of the functions that the normal SMN
protein can. By understanding the differences between the normal full-length SMN protein
and the truncated protein, it is hoped that a new drug discovery platform may be identified.
Additionally, it was previously shown that aminoglycosides increased SMN levels, although
the mechanism was unclear. Now it appears that two distinct mechanisms may be
contributing to the SMN increase: one that produces bona fide SMN protein and an
alternative pathway that generates a stable, but modified SMN protein. This is an important
distinction because the functionality of the modified protein is currently unknown, however,
the increase in true SMN would clearly be a benefit.
Charlotte Sumner (MD, NIH): The goal of a number of potential therapeutic approaches for spinal muscular atrophy (SMA) has focused upon increasing expression from the SMN2
gene. Dr. Sumner has analyzed a family of compounds called HDAC (histone deacetylase)
inhibitors. This group of drugs has previously been shown to function by modifying thestructure of a cell’s DNA. Dr. Sumner is currently analyzing how efficiently HDAC inhibitors
increase SMN2 expression, but she is also focused upon understanding the specific
molecular targets of the HDAC inhibitors. This is important because the identification of
specific factors involved in increasing SMN2 could lead to the development of more efficient
and more specific compounds that could move forward into drug development rapidly.
Arthur Burghes (PhD, Ohio State University): Dr. Burghes has developed a number of
different SMA mouse models that have been instrumental in understanding SMA
development, including mice that represent severe, intermediate, and “mild” SMA.
Currently, these models are being used by researchers around the world to examine
potential SMA therapies. Dr. Burghes’ lab has examined a number of compounds, several of
which will be reported shortly, and that these compounds extend the survival of SMA mice
(ranging from days to weeks). Interestingly, while all of the compounds identified in cell
culture increased SMN protein levels, not all of these compounds increased SMN levels in
mice. This was interesting because it raises the possibility that drugs such as valproic acid
which provide some protection do not elevate SMN, therefore if this drug were combined
with other drugs that did efficiently elevate SMN there might be an even greater degree of
Doug Kerr (MD/PhD, Johns Hopkins Hospital): Dr. Kerr is a pioneer in understanding
how embryonic stem (ES) cells can be used in spinal cord injuries and neurodegenerative
disorders such as SMA. Dr. Kerr has developed a technique to generate SMA motor neurons
from SMA mouse ES cells. SMA motor neuron cultures would represent a highly relevant
context for testing potential SMA therapies and these cells would provide an exciting model
for understanding the defects that lead to motor neuron death in SMA. In a separate
project, Dr. Kerr has made the exciting leap from transplanting ES cell-derived motor
neurons to transplanting these cells and restoring the proper circuitry within a living
organism (a mouse). The transplanted motor neurons can now grow out from the spinal
column and make contact with muscle. Even more remarkable is that the newly transplant
cells can form a competent neuromuscular junction (nerve/muscle interface).As exciting as
this progress has been Dr. Kerr commented that there still are many hurdles which remain
prior to moving this into the clinical realm.
Nick Boulis (MD, The Cleveland Clinic): Dr. Boulis is a neurosurgeon with two primary projects that relate to SMA. First, Dr. Boulis and others are attempting to develop a gene therapy vector that has an increased specificity for neurons. The proteins that make up the
outer surface of the virus can be manipulated in the lab such that an artificial protein is
introduced onto the outside of the virus. This non-viral protein (such as fragments derived
from tetanus toxin C-fragment, rabies G protein, or other experimentally “panned”
peptides) would not interfere with the production of the virus but would result in higher
levels of SMN expression in neurons. Another component of Dr. Boulis’ work involves the
development of an instrument that will be used in spinal cord surgeries. Delivery of
therapeutic agents into the spinal cord such as gene therapy vectors or drugs may prove a
challenging obstacle, however, Dr. Boulis has developed a “scaffold” that will allow
drugs/etc to be delivered directly into the spinal column. The device affixes to a small
section of the spinal cord stabilizes a region of the spine. From this, a very thin cannula
(needle) can be inserted into the spine and drugs can be delivered. Importantly, the relative
position of the cannula can be determined by a series of electrophysiological experiments
which would allow the surgeon to fine tune the position of the cannula.
Alex Mackenzie (MD/PhD, Children’s Hospital of Eastern Ontario): Dr. MacKenzie
demonstrated the power of in silico genomics (sifting through massive amounts of gene
expression data) by identifying well-characterized cell pathways that are upregulated in
concert with SMN2. This was performed in collaboration with a pharmaceutical company
that had the data – but had no interest in SMA. Dr. MacKenzie convinced the company to
share the results and then was able to specifically identify cell pathways that might lead to
SMN2 activation. While the initial results were encouraging, compounds could not be
identified that increased SMN protein levels. However, this does not diminish the enormous
opportunity that exists for “mining” these vast collections of data that could provide insight
into novel compounds that increase SMN2 expression.
Jill Heemskerk (PhD, NIH/NINDS): Dr. Heemskerk’s presentation outlined the structure and goals of the SMA Project, an innovative initiative from the National Institutes of Health.
The goal of the SMA Project is to bring new interventions for SMA clinical trials. The SMA
Project has developed a “business-sensibility” that is designed to streamline the time from
the identification of potential compounds in the laboratory to the testing of these
compounds in clinical trials. A collection of scientists from the pharmaceutical industry,
academic research, nonprofit organizations, and the NIH are attempting to systematically
optimize leads for trial development – an endeavor that is not practical for most academic
labs and not financially interesting to most pharmaceutical companies. To facilitate this, new
discovery tools are being developed within the research community, including motor neuron
cellular models, a SMN ELISA (a rapid means to accurately measure SMN protein levels),
and an inducible SMN mouse model. Currently, the Project has selected two lead
compounds for chemical optimization: Phenyl butyrate (upregulates the SMN2 promoter and
SMN2 splicing), and Indoprofen (increases SMN protein via an unknown post-trascriptional
mechanism). These and other compounds will undergo systematic cycles of development,
including medicinal chemistry, a primary screen, a secondary screen. Multiple rounds of
medicinal chemistry and testing will be done to increase the potency and reduce the side
effects of these drugs to make them suitable for testing as treatments for SMA. The Project
website is at www.smaproject.org.
Thank you to The Ansar Group, Inc. for sponsoring Tuesday night’s Researcher and Panelist Dinner at the Landmark Restaurant and to Ben Aysin for demonstrating Ansar’s ANX 3.0 Autonomic Nervous System Monitoring Software. Ansar is providing the ANX 3.0 lease-free for the FightSMA funded research of Dr. John Bach at the University of Medicine and Dentistry of New Jersey.
|Elliott Androphy, M.D.
Nicholas Boulis, M.D.
Arthur Burghes, Ph.D.
Kenneth Fischbeck, M.D.
Jonathan Glass, M.D.
Jill Heemskerk, Ph.D.
Jean-Pierre Julien, Ph.D.
Petra Kaufmann, M.D.
Hans Keirstead, Ph.D.
Doug Kerr, M.D., Ph.D.
Robert Leshner, M.D.
Christian Lorson, Ph.D.
Alex MacKenzie, M.D., Ph.D.
Karima Ravenell, M.S.
Jeffrey Rothstein, M.D., Ph.D.
Anneliese Schaefer, Ph.D.
David Shine, Ph.D.
Charlotte Sumner, M.D.
Clive Svenden, Ph.D.
Kathy Swoboda, M.D.
Ingrid Tein, M.D.
|University of Massachusetts Medical School
The Cleveland Clinic
Ohio State University
National Institute of Neurological Disorders and Stroke
Emory University School of Medicine
National Institute of Neurological Disorders and Stroke
Laval University, Quebec
University of California-Irvine
Johns Hopkins Hospital
Children’s National Medical Center, Washington D.C.
University of Missouri-Columbia
Children’s Hospital of Eastern Ontario
University of Texas at Southwestern Medical Center
Johns Hopkins Hospital
Washington University School of Medicine
Baylor College of Medicine
National Institute of Neurological Disorders and Stroke
University of Wisconsin-Madison
University of Utah School of Medicine
The Hospital for Sick Children, Toronto
“Thriving with SMA” Panelists Bios
Dr. John Bach – Physiatrist. Dr. Back specializes in rehabilitation of patients with neuromuscular disease, pulmonary disease, and home mechanical ventilation. Dr. Bach has
served on the faculty of the UMDNJ- New Jersey Medical School since 1983.
Dr. Mary Schroth – Pediatric Pulmonologist. Dr. Schroth has been on the faculty of the University of Wisconsin since 1993. She has been instrumental in the development of the
respiratory care program for children with neuromuscular disorders at UW. She also
developed a pediatric multidisciplinary clinic for patients with neuromuscular disease with
colleagues from pediatric rehabilitation medicine and pediatric orthopedic surgery
Dr. Robert Leshner – Pediatric neurologist. Dr. Robert Leshner is professor of neurology and pediatrics at Children’s National Medical Center with a focus on neuromuscular diseases
and muscular dystrophy. Dr. Leshner will serve as the moderator for the panel.
Dr. Jennifer Hewitt – Occupational Therapy. Dr. Hewitt has been providing occupational therapy at Children’s Healthcare of Atlanta to children age birth to 21 years of age. In 2004,
she became certified in Yoga for the Special Child. Since then, she has been providing
therapeutic yoga and functional OT to children on an individual and group basis throughout
Atlanta while also continuing her work at the hospital.
Dr. Chris Makris – Pediatric Pulmonologist. Dr. Makris serves at Children’s Hospital in Birmingham, Alabama. His specialty is sleep disorders. He is medical director for the Sleep
Disorder Center and for the Home Ventilator Program both at Children’s Hospital in
Dr. Eleanore Rothenberg – Psychoanalytic Psychotherapist. Dr. Rothenberg is a licensed clinical social worker and certified group psychotherapist. Dr. Rothenberg is founder of the
Sibling Center for Sisters & Brothers of People with Disabilities (The Sibling Center),
a non-profit organization created to provide services to meet urgent, but unmet, needs of
siblings of people who are mentally, medically, and/or physically challenged. Dr. Rothenberg
specializes in working with adults and children; individuals, groups and couples suffering
from post-traumatic stress disorder, anxiety, depression, eating disorders and complicated
Jennifer Barnes – Speech Language Pathologist. Ms. Barnes is a Level II Speech-Language Pathologist who practices at Children’s Healthcare of Atlanta. Her specialties include cleft-palate-craniofacial disorders and resonance disorders. Her research has focused on attention
and memory deficits associated with traumatic brain injury in adults. She is a strong
advocate for evidence based practice and has co-founded a Journal Club promote evidence
based research and practice in the rehabilitation setting.
Dr. Sherri Katz – Pediatric Respirologist. Dr. Katz is currently an Assistant Professor at the University of Ottawa and serves on staff at Children’s Hospital of Eastern Ontario as a
Pediatric Respirologist. She is the director of the Sleep Laboratory. Dr. Katz has a particular
interest in sleep and neuromuscular disease.
Brian Weaver – Respiratory Therapist. Mr. Weaver is on staff at the University of Medicine and Dentistry of New Jersey. He is a Perinatal/Pediatric Clinical Specialist and Senior
Registered Respiratory Therapist. Mr. Weaver is published and has lectured in therapy for
Type I and Type II SMA patients.
Dr. Kathy Swoboda – Pediatric Neurologist, University of Utah. Dr. Swoboda leads Project Cure and is currently conducting a trial for SMA children with Valproic Acid. Dr. Swoboda
has extensive experience with SMA children both as a clinician and as an investigator. She
will be speaking to nutrition needs as a panelist.