" Non-Invasive Monitoring of NPC Disease via Magnetic Resonance Imaging "
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Abstract: Neimann-Pick Type C (NPC) disease is an inherited genetic defect that results in errant trafficking of intracellular cholesterol and gangliosides.  Although it is rare, NPC is particularly devastating because most NPC sufferers present in early childhood with progressive ataxia and neurodegeneration that leads to death in the second decade of life.  There is currently no effective therapy for NPC disease.  However, development of new therapies is being aided by an increased understanding of the molecular mechanisms underlying NPC as well as the existence of an NPC mouse model. 

A major obstacle to research in NPC therapy is that current non-invasive therapeutic endpoints are limited to qualitative measures of neuromuscular response patterns or delayed onset of weight loss and death.  These endpoints are far from ideal since they are neither sensitive nor quantitative.  A reliable and quantitative method to monitor the progression of NPC disease and its response to successful therapy is greatly needed.  Magnetic resonance imaging (MRI) has potential to be such a method.  It is non-invasive and is equally applicable to investigations of animal models and human patients.  Using diffusion tensor imaging (DTI), a relatively new type of MRI methodology, we have demonstrated that the diffusion of water in white matter regions of the brain of NPC mice is significantly different than that of age-matched littermate controls.  Specifically, the fractional anisotropy (FA) of water, as measured by DTI, is significantly reduced in the white matter of NPC mice.  We have also discovered that T2-relaxation times in these regions are increased by the disease.  These findings correlated with significant reductions of myelin, which is a hallmark of NPC in humans and animal model.  The results of these studies will be presented, as well as the results from a clinical case study.Establishment of quantitative MRI methods that can be used to non-invasively follow the progression of NPC disease in animal models and in humans will expedite the development of effective therapies and add value to future clinical trials.