A new "route forward for therapy" for patients with Duchenne muscular
dystrophy, a degenerative disease that mostly afflicts young boys, has
been reported by Dr.
Kevin Flanigan, principal investigator at the Center
for Gene Therapy at Nationwide Children's Hospital in Columbus,
Ohio. The research, which focuses on developing a therapy for
duplication mutations, has resulted in two recent advances. The first
was the successful creation of a new mouse model of Duchenne that
contains a duplication of exon 2 and the second was the identification
of a novel internal ribosome entry site (IRES) within the 5' coding
region of the DMD gene. Taken together, these advances could provide a
route forward to therapy.
Dr. Flanigan's study was published in the journal Nature Medicine,
and was supported by funding from CurDuchenne,
a national nonprofit that raises awareness and funds research to find a
cure for Duchenne muscular dystrophy. Duchenne is a progressive
muscle-wasting disease that impacts one in 3,500 boys. Boys are usually
diagnosed by age 5, in a wheelchair by 12 and most don't survive their
Skipping of one copy of exon 2 results in a full length "wild-type"
transcript, but skipping of both copies activates the dystrophin IRES,
resulting in the expression of a dystrophin isoform that entirely
corrects most histopathologic markers of damage in the mouse, and
corrects physiologic defects. These results provide Dr. Flanigan's lab
with a pathway forward to treat patients with a duplication of exon 2,
and also patients with mutations within the first 5 exons of the gene.
"CureDuchenne really recognized early on the importance of this work and
we wouldn't be here today without the support of their foundation," said
Dr. Flanigan. "They supported the development of the mouse model and
supported the personnel to work on this research. It is critical for
parents and donors to know that organizations like CureDuchenne vet
projects like this and seek out early phase projects in order to play a
key role in their development."
CureDuchenne has always been interested in rare mutations, and was
pleased when Dr. Flanigan approached the foundation about funding work
on duplication mutations. In 2011, CureDuchenne provided the funding for
Dr. Flanigan to create a new Duchenne mouse model with a duplication
mutation of exon 2, providing the first animal model in which to
directly experiment with exon skipping for duplication mutations.
Duplications account for about six percent of mutations in the gene.
"While this is still early stage research, it expands our understanding
of the genetic underpinnings of Duchenne and, in turn, helps us uncover
new paths toward a cure," said Debra Miller, CEO and founder of
CureDuchenne. "We want a cure for all affected by the disease, and that
is why we have supported all duplication and rare mutations.
CureDuchenne is pleased to see Dr. Flanigan's work progress and is proud
to continue to support his important work."
is a national nonprofit organization located in Newport Beach, Calif.,
dedicated to finding a cure for Duchenne, the most common and most
lethal form of muscular dystrophy. As the leading genetic killer of
young boys, Duchenne affects more than 300,000 boys worldwide.
CureDuchenne has garnered international attention for its efforts to
raise funds and awareness for Duchenne through venture philanthropy.
With the help of CureDuchenne's distinguished international panel of
Scientific Advisors, funds raised by CureDuchenne support the most
promising research aimed at treating and curing Duchenne. To date, seven
CureDuchenne research projects have made their way into human clinical
trials - a unique accomplishment as few health-related nonprofits have
been as successful in being a catalyst for human clinical trials.
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