The Research Institute at Nationwide Children's Hospital notable research accomplishments for 2008, taken from the Annual Report

1. Notable Research
Accomplishments
O
f the more Dr. Brian Kaspar
and his colleagues in
than five the Center for Gene
hundred Therapy reported an
important step forward
scholarly in their ongoing work
to test gene therapeutic
works approaches for muscular
published dystrophy. Muscular
dystrophy, often caused
by faculty at Nationwide Children’s by a mutation in the dystrophin gene, is a serious
Hospital in 2008, the following inherited disorder in which muscles become
progressively weak, damaged and wasted. There
publications are highlighted for a variety is no cure and life expectancy is dramatically
reduced. An obvious therapeutic tactic to treat
of reasons. For example, some report this devastating disease would be to use gene
seminal contributions to the field and therapy to replace the defective dystrophin gene.
are published in leading biomedical While this approach is being developed in the
Center for Gene Therapy, there are complex
journals. Others demonstrate the unique technical challenges unique to the dystrophin
capabilities of scientists at Nationwide gene. Dr. Kaspar conceived of a less complex
molecular approach that involves myostatin, a
Children’s Hospital or emphasize the human protein that naturally acts as a brake on
muscle growth. He reasoned that long-term
outstanding clinical expertise of our
inhibition of myostatin using gene therapy might
faculty. Throughout this report are increase muscle mass. The investigative team used
a single dose of intramuscular adeno-associated
catalogued hundreds of other virus vector housing the myostatin-inhibitor
scientific contributions by our faculty follistatin to assess effects on muscle mass and
function. Significantly increased muscle mass and
to the understanding of pediatric health strength was found in experimental models of
muscular dystrophy. This study advanced the
and disease. As a leading pediatric
group’s progress in designing novel molecular
biomedical research institution, approaches for treating muscular dystrophy in
children. The Center for Gene Therapy is a
Nationwide Children’s Hospital is a sterling example of a translational research group,
major contributor to new knowledge with team members capable of carrying
experimental approaches from the laboratory
that will lead to improvements in the bench to the patient’s bedside.
lives of both ill and well children. – Long-term enhancement of skeletal muscle mass
and strength by single gene administration of
myostatin inhibitors. Proceedings of the National Academy
of Sciences, USA. 2008 Mar 18;105(11):4318-22.
The Research Institute at Nationwide Children’s Hospital :: P A G E 3

2. Christy Collins and outflow tract (LVOT) anomalies in 91
Dr. Dawn Comstock, children. This category of congenital heart
investigators in the defects includes mild lesions like bicuspid aortic
Center for Injury valves, and far more serious defects like congenital
Research and Policy, aortic stenosis, aortic coarctation and hypoplastic
studied the epidemi- left heart syndrome. The latter disorder is fatal
ology of injuries in without urgent intervention in the newborn
high school baseball period. Dr. McBride found mutations in a
players. A novel and major developmental regulatory protein called
innovative feature NOTCH in 15.4% of children with LVOT,
of this research is the use of Reporting Injuries versus 3.9% of controls. These mutations
Online (RIO), a national web-based high school affected NOTCH signaling in in vitro assays,
injury reporting tool recently invented by Dr. proving the biological significance of the
Comstock and collaborators at The Research findings. This important study adds further
Institute. The power of RIO is that large support for a genetic origin for many cases of
numbers of injuries from all over the United congenital heart disease and a hope for early
States can be recorded by coaches and trainers detection, fetal therapy or even prevention.
into the web-based system and then analyzed by
– NOTCH1 mutations in individuals with left
Dr. Comstock and her team. Using RIO, details ventricular outflow tract malformations reduce ligand-
of 131,555 high school baseball injuries were induced signaling. Human Molecular Genetics. 2008 Sep
analyzed in detail. Distinctive findings emerged. 5;17(18):2886-93.
For example, head/face and mouth/teeth injuries
Dr. Jeff Bridge and
for pitchers, infielders and batters were far more
his colleagues in the
common than expected. It is likely that simple
Center for Innovation
protective mechanisms, like mouth guards, could
in Pediatric Practice
protect against many of these injuries.
explored recent suicide
This is the first major research publication trends in adolescents
resulting from the use of RIO. As the program in the United States
is refined and expanded, it will become an using a national
increasingly valuable tool for understanding the database. His findings
epidemiology and mechanics of injury to high were published in a
school athletes and, importantly, how they can peer-reviewed letter to the Journal of the American
be prevented. Medical Association, a leading biomedical journal,
and were featured in many major national media
– Epidemiological features of high school baseball
outlets. Significant excess mortality due to youth
injuries in the United States, 2005-2007. Pediatrics.
2008 Jun;121(6):1181-7. suicide was found during 2004-2005, suggesting
a sustained trend that began the year earlier was
Dr. Kim McBride and
D not a single-year anomaly. This important work
his colleagues in the was a clarion call for additional investigative
Center for Molecular work to understand the origin of this disturbing
and Human Genetics trend in suicide in the United States. Dr. Bridge
have dedicated their is an epidemiologist interested in improving mental
careers to understanding health services for children and adolescents.
the genetic underpin-
– Suicide trends among youths aged 10 to 19 years
nings of congenital
in the United States, 1996-2005. JAMA. 2008 Sep
heart defects, one of 3;300(9):1025-6.
the most common
birth defects affecting children. The investiga-
tive team studied the genetics of left ventricular
P A G E 4 :: The Research Institute at Nationwide Children’s Hospital

3. In 2008, faculty in the
Division of Neurology
contribu
made major contribu-
tions to the field of
pediatric stroke, an
important cause of
chronic morbidity in
children. Dr. Steve
Roach was the lead
author on a highly
visible American Heart Association Scientific
Statement on management of stroke in infants
and children. This comprehensive document was
the first to provide guidelines for diagnosis and
treatment of pediatric stroke.
Led by Dr. Warren Lo,
L
a multidisciplinary team
including faculty from
the Division of
Neurology, the
N
Division of
Hematology, the
Center for Innovation
in Pediatric Practice,
and the Center for
Biobehavioral Health published the first-ever
study of the costs of stroke in children.
Complementing an outstanding clinical program
in stroke care at Nationwide Children’s Hospital,
these scholarly contributions will contribute
to improvements in knowledge relating to this
under-appreciated morbidity in children.
– The cost of pediatric stroke care and rehabilitation.
Stroke. 2008 Jan;39(1):161-5. Epub 2007 Nov 21. :: AS A LEADING PEDIATRIC
– Management of stroke in infants and children: a
scientific statement from a Special Writing Group of BIOMEDICAL RESEARCH
the American Heart Association Stroke Council and
the Council on Cardiovascular Disease in the Young. INSTITUTION, NATIONWIDE
Stroke. 2008 Sep;39(9):2644-91. Epub 2008 Jul 17.
Dozens of additional compelling accomplish- CHILDREN’S HOSPITAL IS A
ments can be found on The Research Institute’s
web site, NationwideChildrens.org/Research. MAJOR CONTRIBUTOR TO
NEW KNOWLEDGE THAT WILL
LEAD TO IMPROVEMENTS
IN THE LIVES OF BOTH ILL
AND WELL CHILDREN.
The Research Institute at Nationwide Children’s Hospital :: P A G E 5