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| Background of the Project |
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Project Cure SMA Mini-Workshop a Huge Success - Spring 2003
by Kristin J. Krosschell, Northwestern University, Evanston, IL. USA
Families of SMA hosted a mini-Project Cure SMA workshop on January
24th and 25th in Salt Lake City, Utah. Team members Tom Crawford, MD,
Kathy Swoboda, MD, Louise Simard, Mary Schroth, MD, Kristin Krosschell,
PT, Natalie Mellem, PT, Jo Anne Maczulski, OT, Johanne Begin, PT, Mark
Wride, Mark Bromberg, MD, Justine Johnson and Adam Craner were joined by
European physicians and therapists Karsten Haug, MD, (Germany) Marion
Main, Physiotherapist, (UK) and Enrico Bertini, MD. ( Italy).
This intense two day workshop focused on the discussion and
refinement of the initial study protocols. The purpose of this initial
study is to establish that the protocol mechanism will be effective for
a clinical study. The project goal is to establish clinical outcome
measures that are reliable and valid to asses change. With the help of
several SMA families from Salt Lake City, Kansas and California, the
team was given hands-on experience and allowed them to evaluate and
observe both the patient and the procedure training and protocol
refinement. It is with thanks to their participation that the workshop
was a huge success. The local Salt Lake City newspapers printed articles
and photographs highlighting the Project Cure SMA meeting as well as SMA
research. NBC TV was there to share the news. It was confirmed that
protocol development was complete and ready to move forward for
multi-centered studies. It is hopeful that these studies will be the
impetus for future clinical drug trials.
Centers that are currently a part of the study are Primary Children’s
Medical Center, Utah; Johns Hopkins, Maryland; University of Wisconsin
Medical Center, Wisconsin, and Hopital Ste Justine, Montreal. Additional
sites are being established in Ohio. The collaboration of International
centers will allow for a uniform and cohesive study.
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August 8, 2003 - Sitting in a Salt
Lake City, Utah, clinic a child and his parents wait. This is a familiar
scene for the family. Different doctors offices, different clinics,
always the same end result. There is no treatment or cure for Spinal
Muscular Atrophy. But today is different; they are here to be a part of
the cure, Project Cure SMA.
Project Cure SMA is a team of physicians
nationally and internationally, supported by Families of Spinal Muscular
Atrophy, and united in their desire to bring safe and effective
treatments to patients as quickly as possible. The primary goals of
Project Cure SMA include the establishment of clinical outcome
measurements in SMA patients and the establishment of a clinical trial
network to facilitate rapid translation of effective treatments to
clinical trials.
"For the last two years, we have been assembling a team of clinicians
from around the world who are at the top of their field in the
evaluation and treatment of SMA patients," said Audrey Lewis, Families
of SMA Executive Director. "Those professionals have been working
diligently to establish clinical outcome measures that are reliable and
valid to assess change."
The first step in the project was to establish both biological and
physiological norms for SMA patients. In January, Families of SMA
hosted a workshop in Salt Lake City where Project Cure Team members from
five countries: Canada, Italy, Germany, the United Kingdom and the
United States all came together for discussion and the refinement of
techniques in the study protocol.
"The team had the opportunity to observe patients during the
evaluation process and discuss refinement of existing protocols," said
team member Kristin Krosschell. "The workshop was a huge success."
At the end of the workshop the Project Cure team confirmed that the
protocol development was complete and ready to move forward toward the
establishment of multicenter trials. Currently there are five centers in
the U.S. participating in the study, one in Canada and a number of
additional International centers have adopted the Project Cure SMA
protocol for their studies. The collaboration of centers allows for
comparison across groups, and will allow for adequate recruitment of
patients for studies.
"As we work together to determine reliable methods of measuring motor
function, pulmonary function and other measures which help to assess the
health of motor neurons in children with SMA, working with the families
to determine protocols that are acceptable for children participating in
such studies is critical" says Kathryn J. Swoboda, M.D., University of
Utah School of Medicine. "The primary motivation for creating Project
Cure SMA is to create a framework where potential medications can be
appropriately tested and evaluated. Safety is a number one priority as
we move toward clinical trials. Even FDA approved medications already on
the market could result in serious medical complications if patients
aren’t monitored appropriately. While many parents are understandably
anxious to try a given supplement or medication that they had heard
about, participating in a controlled study like Project Cure SMA helps
to ensure the safety of the kids, and just as importantly, give us the
information to accurately assess whether or not the drugs are truly
effective."
Project Cure SMA researchers are currently evaluating potential
medications and developing specific protocols for the evaluation of
those medications. The Project Cure SMA team expects to be announcing
preliminary clinical drug trials in the near future.
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PROJECT CURE ANNOUNCES A MAJOR STEP
TOWARDS THE TREATMENT OF SMA
Two Clinical Drug Safety Studies Launched in Children with Spinal
Muscular Atrophy
Salt Lake City, UTAH and Libertyville, ILLINOIS
September 16, 2003 -- Families of Spinal Muscular Atrophy, the
leading funder of Spinal Muscular Atrophy (SMA) research, today
announced the launch of two breakthrough drug safety studies in children
with SMA. These studies are the first two drugs going forward that have
shown increase in SMN protein.
The two studies are drug safety studies that will
examine the tolerability by SMA patients of medications currently
available for treatment of other diseases and conditions. The studies,
conducted by Dr. Kathryn Swoboda and her team at the University of Utah
and Primary Children’s Medical Center, are being funded by Families of
SMA’s Project Cure SMA. This is the first clinical study planned by the
Project Cure SMA team, a collaborative effort of SMA clinicians
worldwide.
Spinal Muscular Atrophy is a genetic disorder
involving the deletion of the Survival Motor Neuron (SMN1) gene on
chromosome 5. This causes a chronic deficiency in the production of SMN
protein, essential to the proper functioning of the motor neurons in the
spinal cord and to the control of muscles in the limbs, neck and chest.
In the US alone there are more than 7 million carriers of the genetic
risk factors for SMA, and the disease affects approximately one in every
6000 live births.
“These are the first two drugs that have shown an
increase in SMN in laboratory studies that are being tested in
children,” said Dr. Swoboda, assistant professor, Departments of
Neurology and Pediatrics, University of Utah School of Medicine.
“Because these medications are currently available, and may occasionally
have significant, potentially life-threatening side-effects, it is
critical that we understand how these medications affect SMA patients so
that we can ensure safety and tolerability before proceeding to bigger
efficacy trials.”
The first study will involve 20 patients: 10 under
the age of two years, and 10 infants who are prenatally identified and
will begin treatment shortly after birth. These patients will be
involved in a study examining the safety of sodium phenylbutyrate.
Preliminary data from an FSMA-funded Italian study, presented by Dr.
Christina Brahe at this year’s FSMA meeting, showed an increase in SMN
genetic message levels in blood cells in a very small group of patients.
The initial safety study will last 6 months.
The second study involves 30 children over the age of
two years. They will receive valproic acid, a medication commonly used
to treat epilepsy, mood disorders, and pain disorders. Laboratory
results presented in the past year by Dr. Kenneth Fischbeck and FSMA-funded
researcher Dr. Brunhilde Wirth have shown that valproic acid may improve
SMN function in cell lines from patients with SMA.
“We are conducting these studies in tandem to gather
preliminary safety results on two different medications that may be
worth further evaluation in the future,” said Dr. Swoboda “We don’t know
at this point whether either or both of these compounds will improve
strength or function in SMA patients. The first step is to make sure
that these treatments are safe. Only after we establish whether they are
safe and well-tolerated is it appropriate to move to a larger trial to
examine potential benefits on motor function.”
Prior to launching these studies Project Cure SMA
team members have been working to establish reliable outcome measures
for clinical trials in SMA patients. Variables currently being measured
include some electrical measures of motor function, pulmonary function
tests, functional outcome scales for motor abilities, and SMN genetic
message and protein levels in cells from SMA patients.
“The dedicated Project Cure clinicians have laid the
groundwork to move forward with these studies. It is a huge step forward
as Dr. Swoboda begins these safety studies which are the beginning for
the day we can say there is a treatment for Spinal Muscular Atrophy"
says Audrey Lewis, executive director of Families of SMA. "I think that
it is so important to remember that while we as parents are desperate
for a treatment we must also remember that the priority in identifying
an effective drug must be safety."
One parent, whose soon-to-be-born child has been
diagnosed with SMA by prenatal testing, and is hoping to participate in
the sodium phenylbuturate study, says “This gives me hope, it will be
wonderful if this helps my child, but it will also be worth it if it
helps other children with SMA.”
About Project Cure SMA
Project Cure SMA is an initiative
Families of SMA began funding in 2000 to create a safe and effective
process for identifying and testing medications that may help to treat
Spinal Muscular Atrophy. The first step of Project Cure was to determine
reliable methods of measuring strength, motor function, pulmonary
function and other measures, which contribute to the health of motor
neurons in children with SMA. Families of SMA continues to fund Project
Cure, which is now conducting safety studies and hopes to pursue
efficacy trials in the future.
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Project Cure SMA Team Members:
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| Dr. Tom Crawford |
Tom Crawford, M.D. has been interested in all
aspects of SMA since 1980. He is currently at Johns Hopkins Hospital
(Baltimore, MD) and continues to be involved in research and
clinical care of children with SMA. Dr. Crawford is a member of FSMA's Scientific Advisory Board and Medical Advisory Board.
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| Dr. Richard Finkel |
Richard Finkel, M.D. is the Director of the
Neuromuscular Clinic and Electromyographer at Children's Hospital of
Philadelphia (CHOP.) He is also the director of the Neurology
Residence Training program, and Clinical Associate Professor in
Pediatrics and Neurology at The University of Pennsylvania, and an
attending staff physician at CHOP. Dr. Finkel is a manuscript
reviewer for Pediatric Neurology and serves on many prominent
committees. |
| Dr. John Kissel |
John Kissel, M.D. is currently Professor of
Neurology and Vice-Chair of the Dept. of Neurology at The Ohio State
University in Columbus, Ohio. He has been on the staff of OSU since
1985 in the Division of Neuromuscular Diseases, and is co-director
of the Muscular Dystrophy Clinic there. Dr. Kissel has published
extensively in a wide range of peripheral nerve, muscle, and
anterior horn cell disorders. He has also participated in clinical
trials involving the inflammatory neuropathies, anterior horn cell
diseases (including SMA) and myasthenia gravis. He is
president-elect of the neuromuscular section of the American Academy
of Neurology, a Fellow in the American Academy of Neurology, and a
member of the American Neurological Association. Dr. Kissel is a
member of FSMA's Medical Advisory Board.
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| Kristin Krosschell |
Kristin Krosschell, MA, PT, has been
a pediatric physical therapist for more than 20 years. She is a
faculty member in the Department of Physical Therapy and Human
Movement Sciences at the Feinberg School of Medicine, Northwestern
University. Her primary focus has been children with neuromuscular
and neurological disorders and muscle diseases. She is member of
FSMA's Medical Advisory Board. |
| Jo Anne Maczulski |
Jo Anne Maczulksi, OT, has been practicing
occupational therapy for 24 years. She received her degree from WSU
and her Masters Degree in Motor Learning from Columbia University.
She has a great deal of experience with chlidren with sensory
integration problems and neuromuscular deficits and diseases. She is
member of FSMA's Medical Advisory Board.
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| Dr. Mary Schroth |
Mary Schroth, M.D. is a Pediatric Pulmonologist and
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. Schroth is a member
of FSMA's Medical Advisory Board. |
| Dr. Louise Simard |
Louise Simard, Ph.D is an Associate Professor
(University of Montreal / Sainte-Justine Hospital Research Centre)
actively involved in SMA research. Her contributions revolve around
molecular diagnostics of SMA, regulation of SNM gene expression and
SMN function in neuronal cells, and more recently, analysis of SMN
nRNA and protein as biochemical markers of SMA type for clinical
trials. Dr. Simard is a member of FSMA's
Medical Advisory Board. |
| Dr. Kathy Swoboda |
Kathryn Swoboda, M.D. is an Assistant professor,
Neurology and Adjunct Assistant Professor, Pediatrics (Medical
Genetics) at the University of Utah School of Medicine. She is a
neurologist and geneticist with expertise in the diagnosis and
management of children with neuromuscular disorders. Dr. Swoboda is
a member of FSMA's Scientific Advisory
Board. |
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