DTI as a tool to identify infants with Krabbe Disease in need of urgent treatment

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Krabbe Disease is an inherited neurodegenerative disease that is rapidly progressive and fatal within 2 years. It is caused by galactocerebrosidase enzyme deficiency (GALC) that results in disruption of myelin metabolism. Once the myelin sheath is destroyed, severe degeneration of mental and motor skills ensue. Umbilical cord transplantation (UCBT) is the only treatment available and is only successful if the patient is treated before symptoms appear. This study will examine the potential for Diffusion Tensor Imaging to be used prognostically for urgent treatment decisions, and as a marker of disease progression associated with motor disability after UCBT. We propose to develop a quantitative method to objectively identify presymptomatic white matter tract abnormalities in at-risk newborns who should receive immediate treatment. This approach will be a key component of a population screening program that identifies babies with low galactocerebrosidase where a family history cannot confirm the diagnosis of infantile Krabbe Disease. Specific Aims: 1) In a prospective study of over 100 babies with low galactocerebrosidase enzyme, determine if DTI can identify which of these newborns will develop infantile Krabbe Disease, 2) To assess how corticospinal white matter tract myelination progresses in the first 24 months of life in infants with low galactocerebrosidase who do not develop infantile Krabbe Disease, 3) To determine, among transplanted children, whether long- term motor function can be predicted by baseline DTI fractional anisotropy measurements. The new knowledge acquired can be immediately translated into clinical practice by correlating DTI measures with disease severity, expected rate of progression and clinical outcomes. The measure has the potential to be validated as a surrogate marker of diseases progression when evaluating the efficacy of new treatments. PUBLIC HEALTH NARRATIVE: Krabbe disease is an inherited neurodegenerative disease that is fatal if untreated within 2 years. Umbilical cord transplantation (UCBT) is only successful if the patient is treated before symptoms appear. This study will examine the potential for Diffusion Tensor Imaging to be used prognostically for treatment decisions, and as a marker of disease progression associated with motor disability after UCBT. [unreadable] [unreadable] [unreadable] [unreadable]