A
novel method of gene therapy is helping children born with a rare
genetic disorder called AADC deficiency that causes severe physical and
developmental disabilities. The study was led by researchers at The Ohio
State University Wexner Medical Center and The Ohio State University
College of Medicine.
Newswise
— COLUMBUS, Ohio – A novel method of gene therapy is helping children
born with a rare genetic disorder called AADC deficiency that causes
severe physical and developmental disabilities. The study, led by
researchers at The Ohio State University Wexner Medical Center and The Ohio State University College of Medicine, offers new hope to those living with incurable genetic and neurodegenerative diseases.
Research findings are published online in the journal Nature Communications.
This
study describes the findings from the targeted delivery of gene therapy
to midbrain to treat a rare deadly neurodevelopmental disorder in
children with a neurogenetic disease, aromatic L-amino acid
decarboxylase (AADC) deficiency characterized by deficient synthesis of
dopamine and serotonin.
Only
about 135 children worldwide are known to be missing the enzyme that
produces dopamine in the central nervous system, which fuels pathways in
the brain responsible for motor function and emotions. Without this
enzyme, children lack muscle control, and are usually unable to speak,
feed themselves or even hold up their head. They also suffer from
seizure-like episodes called oculogyric crises that can last for hours.
“Remarkably,
these episodes are the first symptom to disappear after gene therapy
surgery, and they never return,” said study co-author Dr. Krystof Bankiewicz, professor of neurological surgery at Ohio State College of Medicine who leads the Bankiewicz Lab.
“In the months that follow, many patients experience life-changing
improvements. Not only do they begin laughing and have improved mood,
but many are able to begin speaking and even walking. They are making up
for the time they lost during their abnormal development.”
The
directed gene therapy in seven children ages 4 to 9 who were infused
with the viral vector resulted in dramatic improvement of symptoms,
motor function and quality of life. Six children were treated at UCSF
Benioff Children’s Hospital in San Francisco and one at Ohio State
Wexner Medical Center. This therapeutic modality promises to transform
the treatment of AADC deficiency and other similar disorders of the
brain in the future, Bankiewicz said.
During
the gene therapy surgery, physicians infuse a benign virus programmed
with specific DNA into precisely targeted areas of the brain. The
infusion is delivered extremely slowly as surgeons monitor exactly how
it spreads within the brain using real-time MRI imaging.
“Really,
what we're doing is introducing a different code to the cell,” said Dr.
James “Brad” Elder, director of neurosurgical oncology at Ohio State
Wexner Medical Center’s Neurological Institute.
“And we're watching the whole thing happen live. So we continuously
repeat the MRI and we can see the infusion blossom within the desired
nucleus.”
Researchers
believe this same method of gene therapy can be used to treat other
genetic disorders as well as common neurodegenerative diseases, such as
Parkinson’s and Alzheimer’s disease. Clinical trials are underway to
test this procedure in others living with debilitating and incurable
neurological conditions.
The
directed gene therapy, in these patients, resulted in dramatic
improvement of symptoms, motor function and quality of life. This
therapeutic modality promises to transform the treatment of AADC
deficiency and other similar disorders of the brain in the future.
The
findings described in this study are the culmination of decades of work
by teams from multiple academic institutions, including University of
California San Francisco, Washington University in St. Louis, Medical
Neurogenetics Laboratory in Atlanta, St. Louis Children’s Hospital and
Nationwide Children’s Hospital in Columbus, Ohio.
The research was supported by the National Institute of Neurological Disorders and Stroke and
foundational grants, including the AADC Research Trust, the Pediatric
Neurotransmitter Disease Association and funding from The Ohio State
University.
“This
work provides a framework for the treatment of other human nervous
system genetic diseases. It’s our hope that this will be first of many
ultra-rare and other neurologic disorders that will be treated with gene
therapy in a similar manner,” Bankiewicz said.