Abstract
Niemann-Pick disease type C (NPC) is a rare neurometabolic disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment currently available is miglustat, an iminosugar that inhibits the accumulation of lipid metabolites in neurons and other cells. This longitudinal diffusion tensor imaging (DTI) study examined how the rate of white matter change differed between treated and non-treated adult-onset NPC patient groups. Nine adult-onset NPC patients (seven undergoing treatment with miglustat, two not treated) underwent DTI neuroimaging. Rates of change in white matter structure as indexed by Tract-Based Spatial Statistics (TBSS) of fractional anisotropy were compared between treated and untreated patients. Treated patients were found to have a significantly slower rate of white matter change in the corticospinal tracts, the thalamic radiation and the inferior longitudinal fasciculus. This is further evidence that miglustat treatment may have a protective effect on white matter structure in the adult-onset form of the disease.
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Communicated by: Marc Patterson
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Synopsis
Treatment with miglustat may affect the rate of alteration of white matter structure in progression of Niemann-Pick disease type C.
Author Contributions
Mark Walterfang designed, conceived and implemented the study, including patient recruitment, assessment and data collection. Elizabeth Bowman analysed neuroimaging data. Patricia Desmond assisted with study design and data collection. Dennis Velakoulis assisted with study design and implementation. All authors contributed to preparation and finalisation of the submitted manuscript.
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Mark Walterfang accepts full responsibility for this work, the conduct of the study, had access to the data and controlled the decision to publish.
Competing Interests
Mark Walterfang has served on a scientific advisory board and as a consultant for and received funding for travel from Actelion Pharmaceuticals Ltd, the manufacturer of miglustat. Elizabeth Bowman has received salary support through an unrestricted educational grant to the University of Melbourne from Actelion Pharmaceuticals Ltd. Patricia Desmond and Dennis Velakoulis declare no competing interests.
Funding
This study was supported by an unrestricted educational grant from Actelion Pharmaceuticals. The authors confirm independence from the sponsor; the content of the chapter has not been influenced by this sponsor.
Ethics Approval and Patient Consent
This study was approved by the Melbourne Health Research and Ethics Committee. All subjects provided informed consent.
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Bowman, E.A., Velakoulis, D., Desmond, P., Walterfang, M. (2017). Longitudinal Changes in White Matter Fractional Anisotropy in Adult-Onset Niemann-Pick Disease Type C Patients Treated with Miglustat. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 39. JIMD Reports, vol 39. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2017_42
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DOI: https://doi.org/10.1007/8904_2017_42
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