An $8 million gift from the Foundation
of Caring will help CHOC Children’s advance research for a rare lysosomal
storage disease, ultimately leading to an improved understanding and more
The gift will support CHOC researchers
working to develop next-generation therapies for Pompe disease, a lysosomal
storage disease wherein glycogen builds up in the body’s cells and causes
life-threatening heart failure and muscle weakness in affected babies. In honor
of the gift, the program will be named the Foundation of Caring Lysosomal Storage
Disorder Program at CHOC Children’s.
“This incredibly generous gift from the Foundation of Caring will help accelerate our work to unlock the challenges of Pompe disease and other lysosomal storage disorders, advancing our vision to develop permanent cures for patients with these conditions,” said Dr. Raymond Wang, a CHOC metabolic disorders specialist and director of the Foundation of Caring Lysosomal Storage Disorder Program. “We’re so tremendously grateful to have the Foundation of Caring’s support in CHOC’s goal to protect the magic of childhood.”
Dr. Wang’s work around Pompe disease
drew the attention of the Foundation of Caring several years ago, when he began
treating the great-granddaughter of the Foundation’s founder after she was
diagnosed with the condition.
With previous support from the Foundation
of Caring, Dr. Wang and his team have already made significant strides in its study
of Pompe disease, having built a growing research team that’s used CRISPR/Cas9
technology to edit the genome to create animal models of Pompe disease. The
Foundation of Caring’s gift will allow Dr. Wang and his team to expand upon
this work and use CRISPR to cure Pompe disease and lysosomal storage disorders.
“We are so pleased to support the
important work of Dr. Wang and his team at CHOC to help find better treatment
or, even better, a cure for Pompe disease for patients affected by the condition
worldwide,” said the Foundation of Caring Board of Directors.
CHOC Children’s Hospital recently administered the first ever in-human dosing
of gene therapy for Hurler Syndrome, the severe form of mucopolysaccharidosis
type I (MPS I), a rare and progressive lysosomal storage disease.
successful, the gene therapy could present an alternative treatment for Hurler
Syndrome, which currently calls for a stem cell transplant for children younger
than 2 ½. While stem cell transplants are well-proven to help prevent most of
the neurologic decline that happens to untreated MPS I patients, the procedure
poses significant risks.
Patients with MPS I have a
genetic mutation that leads to a deficiency in alpha-L-iduronidase. This enzyme
helps break down chemicals called glycosaminoglycans, specifically dermatan and
heparin sulfate, the buildup of which can ultimately cause enlarged organs and
tissues, heart valve thickening, spinal cord compression, hydrocephalus and progressive
loss of intellectual milestones.
The hope is that the gene therapy – RGX-111, which is produced by REGENXBIO Inc. – will equip the patient’s brain cells with the information needed to make working alpha-Liduronidase enzyme to stop the glycosaminoglycans from building in the brain, says Dr. Raymond Wang, a CHOC pediatric metabolic disorders specialist and the study’s lead investigator.
The therapy was
administered through a cervical puncture in the neck. With three-dimensional
visualization and guidance from a computed tomography scanner, CHOC
interventional radiologist Dr. Tammam Beydoun carefully inserted the needle into
the fluid-filled space at the junction of the spinal cord and brain stem. Then,
Dr. Wang administered the gene therapy.
“I could not have
asked for a better implementation of everything we had planned for many months,”
Dr. Wang says. “I am so grateful for such an awesome team of people working
together for one common goal.”
Dr. Wang says the patient will be monitored indefinitely, with clinicians tracking the child’s cognitive and physical development, as well as measuring the quantity of alpha-L-iduronidase in the child’s body and spinal fluid to determine whether glycosaminoglycans dermatan and heparin sulfate are being broken down.
“I cannot guarantee if the
gene therapy is going to work, but the alternative was to watch and let this
patient get worse and worse and worse,” said Dr. Raymond Wang. “We’ve got to
Babies with MPS I show no
signs of the condition upon birth. To this end, MPS I was added to the list of
conditions tested for in California’s Newborn Screening Program in 2018. But
even with enzyme replacement therapy treatment, recommended to begin before age
2, the disease continues to progress, Dr. Wang says.
“Patients will reach a plateau in developmental milestones, and then they’ll start losing milestones,” he says. “Once they could speak, they lose the ability to speak. Once they were able to walk, they lose ability to walk. Then it gets to be really heartbreaking: Once they could eat, then they can’t eat anymore.”
Many patients ultimately rely
on feeding tubes, while often enduring airway problems, cardiac disease and
hydrocephalus. Quality of life is typically poor, Dr. Wang says.
Not only could a
successful outcome in this investigation dramatically change the course of a
patient’s life, but it could also pave the way for future gene therapy for
additional patients with rare diseases at CHOC, Dr. Wang says.
“This is an opening chapter for a very cool story,” Dr. Wang says.