Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease

Forbes D. Porter, David E. Scherrer, Michael H. Lanier, S. Joshua Langmade, Vasumathi Molugu, Sarah E. Gale, Dana Olzeski, Rohini Sidhu, Dennis J. Dietzen, Rao Fu, Christopher A. Wassif, Nicole M. Yanjanin, Steven P. Marso, John House, Charles Vite, Jean E. Schaffer, Daniel S. Ory

Research output: Contribution to journalArticle

210 Citations (Scopus)

Abstract

Niemann-Pick type C1 (NPC1) disease is a rare progressive neurodegenerative disorder characterized by accumulation of cholesterol in the endolysosomes. Previous studies implicating oxidative stress in NPC1 disease pathogenesis raised the possibility that nonenzymatic formation of cholesterol oxidation products could serve as disease biomarkers. We measured these metabolites in the plasma and tissues of the Npc1-/- mouse model and found several cholesterol oxidation products that were elevated in Npc1-/- mice, were detectable before the onset of symptoms, and were associated with disease progression. Nonenzymatically formed cholesterol oxidation products were similarly increased in the plasma of all human NPC1 subjects studied and delineated an oxysterol profile specific for NPC1 disease. This oxysterol profile also correlated with the age of disease onset and disease severity. We further show that the plasma oxysterol markers decreased in response to an established therapeutic intervention in the NPC1 feline model. These cholesterol oxidation products are robust blood-based biochemical markers for NPC1 disease that may prove transformative for diagnosis and treatment of this disorder, and as outcome measures to monitor response to therapy.

Original languageEnglish (US)
Article number56ra81
JournalScience Translational Medicine
Volume2
Issue number56
DOIs
StatePublished - Nov 3 2010

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Niemann-Pick Diseases
Type C Niemann-Pick Disease
Biomarkers
Cholesterol
Felidae
Age of Onset
Neurodegenerative Diseases
Disease Progression
Oxidative Stress
Outcome Assessment (Health Care)
Therapeutics
Oxysterols

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Porter, F. D., Scherrer, D. E., Lanier, M. H., Langmade, S. J., Molugu, V., Gale, S. E., ... Ory, D. S. (2010). Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease. Science Translational Medicine, 2(56), [56ra81]. https://doi.org/10.1126/scitranslmed.3001417

Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease. / Porter, Forbes D.; Scherrer, David E.; Lanier, Michael H.; Langmade, S. Joshua; Molugu, Vasumathi; Gale, Sarah E.; Olzeski, Dana; Sidhu, Rohini; Dietzen, Dennis J.; Fu, Rao; Wassif, Christopher A.; Yanjanin, Nicole M.; Marso, Steven P.; House, John; Vite, Charles; Schaffer, Jean E.; Ory, Daniel S.

In: Science Translational Medicine, Vol. 2, No. 56, 56ra81, 03.11.2010.

Research output: Contribution to journalArticle

Porter, FD, Scherrer, DE, Lanier, MH, Langmade, SJ, Molugu, V, Gale, SE, Olzeski, D, Sidhu, R, Dietzen, DJ, Fu, R, Wassif, CA, Yanjanin, NM, Marso, SP, House, J, Vite, C, Schaffer, JE & Ory, DS 2010, 'Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease', Science Translational Medicine, vol. 2, no. 56, 56ra81. https://doi.org/10.1126/scitranslmed.3001417
Porter, Forbes D. ; Scherrer, David E. ; Lanier, Michael H. ; Langmade, S. Joshua ; Molugu, Vasumathi ; Gale, Sarah E. ; Olzeski, Dana ; Sidhu, Rohini ; Dietzen, Dennis J. ; Fu, Rao ; Wassif, Christopher A. ; Yanjanin, Nicole M. ; Marso, Steven P. ; House, John ; Vite, Charles ; Schaffer, Jean E. ; Ory, Daniel S. / Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease. In: Science Translational Medicine. 2010 ; Vol. 2, No. 56.
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