Eva Morava-Kozicz, M.D., Ph.D. received a $5 million grant from the National Institutes of Health to study frontiers in congenital disorders of glycosylation (CDG). These disorders often cause serious, sometimes fatal, malfunction of several different organ systems in affected infants.

“This grant will allow us to leverage cross-disciplinary, team-based clinical science to address decades of unresolved questions, increase clinical trial readiness, advance and share knowledge, develop treatment, and meet unmet patient needs,” says Dr. Morava-Kozicz.

Dr. Morava-Kozicz conducts translational research in congenital disorders of glycosylation and mitochondrial disorders and is actively involved in developing dietary therapies in genetic disorders. In addition to her roles as a pediatrician, geneticist and metabolic specialist, she has decades of experience in the diagnostics, follow-up and treatment in inborn errors of metabolism, especially congenital disorders of glycosylation and in mitochondrial disorders.

As principal investigator of the multicenter study on the natural history of congenital disorders of glycosylation, Dr. Morava-Kozicz knows first-hand what gaps need to be addressed.

In response to this need Dr. Morava-Kozicz established a nation-wide network of 10 regional centers to:  

• Define the natural history, validate patient reported outcomes and share CDG knowledge
• Develop and validate new biochemical diagnostic techniques and therapeutic biomarkers to increase clinical trial readiness
• Evaluate whether dietary treatments restore appropriate glycosylation to improve clinical symptoms and quality of life

The grant supports the new Frontiers in Congenital Disorders of Glycosylation consortia, through the Rare Diseases Clinical Research Network (RDCRN), aimed at fostering collaborative research among scientists to better understand how rare diseases progress and to develop improved approaches for diagnosis and treatment.

Congenital disorders of glycosylation are a group of over 150 inherited metabolic disorders affecting several steps of the pathway involved in the glycosylation of proteins. They typically present as multi-systemic disorders with a broad clinical spectrum including, but not limited to, developmental delay, an abnormally low level of muscle tone, abnormal magnetic resonance imaging findings, skin manifestations, and hemorrhaging or clotting disorders. Neurological abnormalities may also be present. There is considerable variation in the severity of this group of diseases ranging from a mild presentation in adults to severe multi-organ dysfunctions causing infantile death.

An important focus of the award is on clinical trial readiness. In order to be prepared to conduct clinical trials the consortia needs to have strong natural history studies that show how the disease progresses. This will lead to ways to measure outcomes of treatments and biomarker studies that provide indicators of how a drug is working in patients.

Collaboration is key. The consortium includes numerous partner research teams from different sites, along with rare disease patients and advocacy groups as research partners. Scientists from different institutions will come together to share patients, data, experience and resources.

Investigator partners include Children Hospital of Philadelphia, Seattle Children’s and Sanford Burnham Prebys Medical Discovery Institute.

Co-investigators include Baylor College of Medicine; Boston Children’s Hospital; Children’s Hospital of Colorado; Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center; National Human Genome Institute; Seattle Children’s Hospital; Tulane University Medical School; University of Alabama; University of Colorado, University of Minnesota Masonic Children’s Hospital; and University of Utah.

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