The Foundation recognizes that development of clinician researchers is extremely important to the field of child neurology. A junior faculty member who has developed clinical research skills, and has a plan for further development of that research or has basic science research skills related to child neurology, and who has a plan to translate the new knowledge into clinical care for children with neurologic diseases is eligible for this award. Candidates for the award are asked to submit brief letters of intent which will be scored by members of the CNF Scientific Award Committee. The committee that reviews the applications includes child neurologists who are also successful scientists, including several who have been recipients of CNF awards. In addition to scientific criteria such as the soundness of the hypothesis, feasibility, and relevance to clinical pediatric neurological disorders, reviewers look for evidence that the award will have a major career impact.
The Shields Grant is supported by the Winokur Family Foundation.
University of Rochester
“Cell-based therapy for Pelizaeus-Merzbacher disease”
This research project aims to develop a cell-based treatment strategy for Pelizaeus-Merzbacher disease (PMD), a severe pediatric disorder of myelin caused by mutations in the proteolipid protein gene (PLP1). By transplanting genetically corrected cells from affected patients in a murine model of PMD, we will test their ability to rescue the phenotype and produce normal myelin. We will use induced pluripotent stem cells from patients with duplications and missense mutations in the PLP1 gene, correct the mutations by using gene-editing techniques and subsequently differentiate those to oligodendroglial fate. After intracerebral transplantation in a murine model of PMD, we will evaluate their motor performance and posteriorly the histology of engrafted cells. If this study is successful, this study will provide a proof of principle that autologous cell transplantation can be a feasible strategy for treatment of congenital disorders of myelin.
My career goal as a clinician-scientist is to bridge basic research and clinical work, to establish new treatment strategies for pediatric white matter disorders for which no cure is presently available. The Shields Award represents an important step towards this goal, by supporting my research project that will focus on Pelizaeus-Merzbacher disease (PMD). Success of this pre-clinical study will advance clinical translation of cell-based therapies that can be applied not only to PMD but potentially also to other leukodystrophies.
Acting Assistant Professor
Seattle Children’s Hospital/Seattle Children’s Research Institute
One in a thousand newborn infants is diagnosed with hydrocephalus before they even leave the hospital, which can leave their families blindsided. My research proposal seeks to address basic questions about hydrocephalus in children: why it happens, how best to treat it, and what it means for a child’s future. There are three parts to my project: First, I will use MRI-based techniques to explore the relationship between the shape of a child’s brain and the way that cerebrospinal fluid and blood flow within and around it. Second, I will collect detailed clinical information about how children with different types of hydrocephalus develop physically and cognitively, and how they respond to various types of surgery. Finally, I will use these results to guide genomic investigations of the factors that give rise to different types of hydrocephalus, and to differences in clinical outcome. The goal of my work is a deeper understanding of why hydrocephalus develops, a better grasp of its clinical implications, and a new sense of how to tailor treatment to each individual child.