Evidence map›Paper›PMID 27307499›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2016

Cerebrospinal Fluid Calbindin D Concentration as a Biomarker of Cerebellar Disease Progression in Niemann-Pick Type C1 Disease.

Allison Bradbury, Jessica Bagel, Maureen Sampson, Nicole Farhat, Wenge Ding, Gary Swain, Maria Prociuk, Patricia O'Donnell, Kenneth Drobatz, Brittney Gurda and 4 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 43 citations in OpenAlex.

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  15. Altered protein secretion in Batten disease.Disease models & mechanisms · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 2 countries.

Allison BradburyDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.B., J.B., W.D., G.S., M.P., P.O., K.D., B.G., C.V.); Division of Intramural Research, National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland (M.S., A.R.); and Division of Translational Research, National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland (N.F., C.W., F.P.) brada@vet.upenn.edu.
Jessica BagelDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.B., J.B., W.D., G.S., M.P., P.O., K.D., B.G., C.V.); Division of Intramural Research, National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland (M.S., A.R.); and Division of Translational Research, National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland (N.F., C.W., F.P.).
Maureen SampsonDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.B., J.B., W.D., G.S., M.P., P.O., K.D., B.G., C.V.); Division of Intramural Research, National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland (M.S., A.R.); and Division of Translational Research, National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland (N.F., C.W., F.P.).
Nicole FarhatDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.B., J.B., W.D., G.S., M.P., P.O., K.D., B.G., C.V.); Division of Intramural Research, National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland (M.S., A.R.); and Division of Translational Research, National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland (N.F., C.W., F.P.).
Wenge DingDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.B., J.B., W.D., G.S., M.P., P.O., K.D., B.G., C.V.); Division of Intramural Research, National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland (M.S., A.R.); and Division of Translational Research, National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland (N.F., C.W., F.P.).
Gary SwainDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.B., J.B., W.D., G.S., M.P., P.O., K.D., B.G., C.V.); Division of Intramural Research, National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland (M.S., A.R.); and Division of Translational Research, National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland (N.F., C.W., F.P.).
Maria ProciukDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.B., J.B., W.D., G.S., M.P., P.O., K.D., B.G., C.V.); Division of Intramural Research, National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland (M.S., A.R.); and Division of Translational Research, National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland (N.F., C.W., F.P.).
Patricia O'DonnellDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.B., J.B., W.D., G.S., M.P., P.O., K.D., B.G., C.V.); Division of Intramural Research, National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland (M.S., A.R.); and Division of Translational Research, National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland (N.F., C.W., F.P.).
Kenneth DrobatzDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.B., J.B., W.D., G.S., M.P., P.O., K.D., B.G., C.V.); Division of Intramural Research, National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland (M.S., A.R.); and Division of Translational Research, National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland (N.F., C.W., F.P.).
Brittney GurdaDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.B., J.B., W.D., G.S., M.P., P.O., K.D., B.G., C.V.); Division of Intramural Research, National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland (M.S., A.R.); and Division of Translational Research, National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland (N.F., C.W., F.P.).
Christopher WassifDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.B., J.B., W.D., G.S., M.P., P.O., K.D., B.G., C.V.); Division of Intramural Research, National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland (M.S., A.R.); and Division of Translational Research, National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland (N.F., C.W., F.P.).
Alan RemaleyDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.B., J.B., W.D., G.S., M.P., P.O., K.D., B.G., C.V.); Division of Intramural Research, National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland (M.S., A.R.); and Division of Translational Research, National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland (N.F., C.W., F.P.).
Forbes PorterDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.B., J.B., W.D., G.S., M.P., P.O., K.D., B.G., C.V.); Division of Intramural Research, National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland (M.S., A.R.); and Division of Translational Research, National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland (N.F., C.W., F.P.).
Charles ViteDepartment of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (A.B., J.B., W.D., G.S., M.P., P.O., K.D., B.G., C.V.); Division of Intramural Research, National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland (M.S., A.R.); and Division of Translational Research, National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland (N.F., C.W., F.P.).
University of Pennsylvania · USNational Institute of Child Health · HUEunice Kennedy Shriver National Institute of Child Health and Human Development · USNational Heart Lung and Blood Institute · USNational Institutes of Health · US

Funding

Inborn Errors of Cholesterol SynthesisZIAHD000139 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI PORTER, FORBES · 2009 to 2019
$11.7M
Referral Ctr-Animal models of human genetic diseaseP40OD010939 · OD · UNIVERSITY OF PENNSYLVANIA · PI CASAL, MARGRET L · 2012 to 2023
$7.9M
Clinical Investigations of Niemann-Pick Disease, type CZIAHD008824 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI PORTER, FORBES · 2009 to 2019
$5.2M
Intrathecal cyclodextrin therapy of feline Niemann-Pick type C diseaseR01NS073661 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI VITE, CHARLES H · 2011 to 2015
$1.7M
NIH HHS P40 OD010939NINDS NIH HHS R01 NS073661
6 · The paper itself

Abstract

Niemann-Pick type C (NPC) 1 disease is a rare, inherited, neurodegenerative disease. Clear evidence of the therapeutic efficacy of 2-hydroxypropyl-β-cyclodextrin (HPβCD) in animal models resulted in the initiation of a phase I/IIa clinical trial in 2013 and a phase IIb/III trial in 2015. With clinical trials ongoing, validation of a biomarker to track disease progression and serve as a supporting outcome measure of therapeutic efficacy has become compulsory. In this study, we evaluated calcium-binding protein calbindin D-28K (calbindin) concentrations in the cerebrospinal fluid (CSF) as a biomarker of NPC1 disease. In the naturally occurring feline model, CSF calbindin was significantly elevated at 3 weeks of age, prior to the onset of cerebellar dysfunction, and steadily increased to >10-fold over normal at end-stage disease. Biweekly intrathecal administration of HPβCD initiated prior to the onset of neurologic dysfunction completely normalized CSF calbindin in NPC1 cats at all time points analyzed when followed up to 78 weeks of age. Initiation of HPβCD after the onset of clinical signs (16 weeks of age) resulted in a delayed reduction of calbindin levels in the CSF. Evaluation of CSF from patients with NPC1 revealed that calbindin concentrations were significantly elevated compared with CSF samples collected from unaffected patients. Off-label treatment of patients with NPC1 with miglustat, an inhibitor of glycosphingolipid biosynthesis, significantly decreased CSF calbindin compared with pretreatment concentrations. These data suggest that the CSF calbindin concentration is a sensitive biomarker of NPC1 disease that could be instrumental as an outcome measure of therapeutic efficacy in ongoing clinical trials.

Indexed as

Disease Progression2-Hydroxypropyl-beta-cyclodextrinAdolescentAdultAnimalsbeta-CyclodextrinsBiomarkersCalbindin 1CatsChildChild, PreschoolFemaleGlycosphingolipidsHumansInfantMale2-Hydroxypropyl-beta-cyclodextrinbeta-CyclodextrinsBiomarkersCalbindin 1Glycosphingolipids

Identifiers

PMID27307499
PMCPMC4959104
OpenAlexW2427881236

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.