Pediatric Rare Disease Research

CHOC offers access to cutting-edge pediatric research and clinical trials that can't be found anywhere else.
Long live childhood

At the CHOC Research Institute, we know a rare disease diagnosis can be devastating for families. Our work focuses on developing and improving treatments for children with rare conditions that either do not respond to traditional treatments or that do not have current treatments.

Our innovative research in rare diseases spans from our Metabolic Rare Disease Program (MRDP) – which comprises about 80% of the pediatric rare diseases we encounter at CHOC – to rare diseases in hematology, neurology, oncology and neuro-oncology, cardiology, pulmonology, infectious disease, gastroenterology, critical care and urology.

Metabolic Rare Disease Research at CHOC

Our Metabolic Rare Disease Program (MRDP) is among the first comprehensive programs in the U.S. to offer the full continuum of services for children with rare metabolic conditions. Patients and their families have direct access to board-certified specialists, nurse practitioners, dietitians, genetic counselors, nurses and social workers, as well as diagnostic and research laboratory scientists, PhDs and doctoral students who can provide the latest therapies, including clinical trials. Our program advances research and education, and streamlines access to inpatient and outpatient services, resulting in better outcomes for children with rare diseases.

All our research activities are focused on rare or ultra-rare diseases and include:

  • Adrenoleukodystrophy (ALD): ALD is a metabolic disease that can be devastating for patients and families if not identified and treated early. Since the start of the State of CA Newborn Screening Program, we have established a multidisciplinary clinic for clinical care and research that includes pediatric metabolic, neurology and endocrinology experts, as well as genetic counselors, case managers and social workers.
  • Glycogen Storage Disease (GSD)
  • Inborn Errors of Metabolism (IEM) Clinic
  • Lysosomal Storage Diseases (LSD)
  • Multidisciplinary Mucopolysaccharidosis Center
  • Neurometabolic Disorders
  • Newborn Screening: The MRDP program is the designated Orange County center for the evaluation and treatment of children with a presumed metabolic disease through the State of California Newborn Screening Program. MRDP has been instrumental in developing guidelines for the confirmatory testing of these conditions and has published extensively in this subject.
  • Phenylketonuria (PKU)

Our Metabolic Rare Disease Research Model

The CHOC MRDP includes four arms: Clinical Support, Basic Science Research, Translational Science Research and Clinical Trials. Together, they create our bed-bench-bed research model, where children and families are always at the center of our work. Focusing on each individual patient, we conduct research to bring cutting-edge treatments back to the bedside of patients and their families, to improve outcomes and increase quality of life.

Our clinics are typically the “first stop,” where patients with rare metabolic diseases are evaluated, and biochemical and genetic diagnostic workup is done. Patients with disorders difficult to diagnose, as well as those affected by disorders that fit our existing programs, are considered for research protocols through the Basic Science Research arm. The Basic Science Laboratories investigate the mechanisms of the diseases and test potential treatments in cell cultures. Then, our Translational Science Research arm focuses on providing the pre-clinical data needed for FDA applications so that Clinical Trials of novel therapies may begin. Findings from Clinical Trials can then be used to innovate care for patients of our current rare disease clinics, as well as provide care for previously untreated rare disorders internationally.

Scientific Rare Disease Research at CHOC

  • Lysosomal Storage Disease Laboratory: The Lysosomal Storage Disease Laboratory (LSD-Lab) aims to develop more effective treatments for lysosomal storage disorders, beyond the currently available hematopoietic stem cell transplantation (HSCT) and intravenous enzyme replacement therapy (ERT). Specific projects include:
    • Mucopolysaccharidosis (MPS): Research focuses on defining biomarkers that cause progression or improvement of cardiovascular disease. We have also advanced projects to study the use of combined intra-articular/intravenous/intracranial gene therapy for MPS I disease.
    • Pompe Disease: We are utilizing cutting edge CRISPR genome editing to permanently correct the severe myopathy in Pompe disease mouse models
  • Laboratory for Energy Metabolism (E-Lab): The E-Lab studies diseases affecting mitochondrial energy production. The E-Lab’s state-of-the-art equipment includes a bioinformatics workstation used for the analysis of whole exome, whole genome and whole transcriptome sequencing; tissue culture facilities; a hypoxia environmental incubation system; a SeaHorse bioanalyzer; a fluorescent microscope; a fluorescence-activated cell sorter; and others. These sophisticated pieces of equipment are used to uncover new gene defects, characterize diseases at the cellular level and investigate new therapies. Current projects include:
    • DARS2 defects: Defects in the DARS2 gene cause Leukoencephalopathy with Brain Stem Involvement and Lactic acid elevation (LBSL). This is a mitochondrial disorder for which there is currently no effective treatment.
    • Mitochondrial DNA depletion syndromes: E-lab research is focused on understanding why different organs (i.e. brain or liver) are selectively affected in some of these diseases. We are also exploring the metabolism of a co-factor (BH4) in these disorders.
  • The Laboratory for Cellular Models of Disease (CM-Lab): The CM-Lab specializes in differentiating patient skin cells into pluripotent stem cells, which can then be further differentiated into organ-specific cell types (i.e. neurons). These newly generated cells are used to target tissue specific treatments.
  • The Center for Advancing Rare disease Editing (CARE): This Center uses genome-editing technology to generate, characterize and treat animal models with rare diseases featuring known pathogenic mutations. The CARE laboratory has created the first mouse model for Pompe Disease (PD) and is applying the same principles of CRISPR-Cas9 technology to study Sialic Acid Storage Disorders (SASD).
  • The Drug and Cell Discovery Laboratory (DC-Lab): The DC-Lab aims to develop therapies for rare disorders. Current projects include the use of cell culture and cell sorting systems to select cells for transplantation in the treatment of lysosomal Storage Disorders and to explore small-molecule (drug) approaches for mitochondrial disease therapy.
The MRDP actively participates in clinical trials collaborating with different centers worldwide. They include, among others: