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8OHdG is not a biomarker for Huntington disease state or progression

Identifieur interne : 000639 ( Pmc/Corpus ); précédent : 000638; suivant : 000640

8OHdG is not a biomarker for Huntington disease state or progression

Auteurs : Beth Borowsky ; John Warner ; Blair R. Leavitt ; Sarah J. Tabrizi ; Raymund A. C. Roos ; Alexandra Durr ; Chris Becker ; Cristina Sampaio ; Allan J. Tobin ; Howard Schulman

Source :

RBID : PMC:3716347

Abstract

Objective:

To evaluate plasma 8-hydroxy-deoxy-guanosine (8OHdG) levels as a potential biomarker of premanifest and early Huntington disease (HD).

Methods:

Personnel from 2 independent laboratories quantified 8OHdG in blinded longitudinal plasma samples taken 24 months apart from 160 TRACK-HD participants, as well as samples containing control plasma with added (“spiked”) 8OHdG. One laboratory used a liquid chromatography–electrochemical array (LCECA) assay, and the other used liquid chromatography–mass spectrometry (LCMS).

Results:

The LCMS assay was more accurate than the LCECA assay for measurements of “spiked” 8OHdG levels in plasma. Neither assay demonstrated cross-sectional differences in plasma 8OHdG among controls, premanifest HD, and early symptomatic HD. Similarly, neither assay showed longitudinal changes in any disease group over 24 months.

Conclusions:

Plasma concentration of 8OHdG is not a biomarker of disease state or progression in HD. We recommend that future putative biomarker studies use blinded sample analysis, standard curves, independent analytical methods, and strict quality control of sample collection and storage.


Url:
DOI: 10.1212/WNL.0b013e318293e1a1
PubMed: 23616162
PubMed Central: 3716347

Links to Exploration step

PMC:3716347

Le document en format XML

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<title>Objective:</title>
<p>To evaluate plasma 8-hydroxy-deoxy-guanosine (8OHdG) levels as a potential biomarker of premanifest and early Huntington disease (HD).</p>
</sec>
<sec>
<title>Methods:</title>
<p>Personnel from 2 independent laboratories quantified 8OHdG in blinded longitudinal plasma samples taken 24 months apart from 160 TRACK-HD participants, as well as samples containing control plasma with added (“spiked”) 8OHdG. One laboratory used a liquid chromatography–electrochemical array (LCECA) assay, and the other used liquid chromatography–mass spectrometry (LCMS).</p>
</sec>
<sec>
<title>Results:</title>
<p>The LCMS assay was more accurate than the LCECA assay for measurements of “spiked” 8OHdG levels in plasma. Neither assay demonstrated cross-sectional differences in plasma 8OHdG among controls, premanifest HD, and early symptomatic HD. Similarly, neither assay showed longitudinal changes in any disease group over 24 months.</p>
</sec>
<sec>
<title>Conclusions:</title>
<p>Plasma concentration of 8OHdG is not a biomarker of disease state or progression in HD. We recommend that future putative biomarker studies use blinded sample analysis, standard curves, independent analytical methods, and strict quality control of sample collection and storage.</p>
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<name>
<surname>Borowsky</surname>
<given-names>Beth</given-names>
</name>
<degrees>PhD</degrees>
<author-comment content-type="disclosure">
<p>
<list list-type="order">
<title>Scientific Advisory Boards:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Gifts:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Funding for Travel or Speaker Honoraria:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Editorial Boards:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Patents:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Publishing Royalties:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Employment, Commercial Entity:</title>
<list-item>
<p>CHDI Management/Foundation, Director of Translational Medicine</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Consultancies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Speakers' Bureaus:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Other Activities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Clinical Procedures or Imaging Studies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Commercial Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Government Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Academic Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Foundations and Societies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>License Fee Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Royalty Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Research Sponsor:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Legal Proceedings:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Warner</surname>
<given-names>John</given-names>
</name>
<degrees>PhD</degrees>
<author-comment content-type="disclosure">
<p>
<list list-type="order">
<title>Scientific Advisory Boards:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Gifts:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Funding for Travel or Speaker Honoraria:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Editorial Boards:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Patents:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Publishing Royalties:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Employment, Commercial Entity:</title>
<list-item>
<p>CHDI, Director of Biostatistics</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Consultancies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Speakers' Bureaus:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Other Activities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Clinical Procedures or Imaging Studies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Commercial Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Government Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Academic Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Foundations and Societies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>License Fee Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Royalty Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Research Sponsor:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Legal Proceedings:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Leavitt</surname>
<given-names>Blair R.</given-names>
</name>
<degrees>MD</degrees>
<author-comment content-type="disclosure">
<p>
<list list-type="order">
<title>Scientific Advisory Boards:</title>
<list-item>
<p>1. Member, Scientific Advisory Board, Siena BioTech SbA, Italy - 2010-present 2. member, DSMB Reach2HD Study, Prana</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Gifts:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Funding for Travel or Speaker Honoraria:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Editorial Boards:</title>
<list-item>
<p>Founding Editor and Co-Editor-in-Chief, “Journal of Huntington's Disease”, 2011- present.</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Patents:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Publishing Royalties:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Employment, Commercial Entity:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Consultancies:</title>
<list-item>
<p>1. 43 Expert Consultant Presentation: Laxdale, New Drug Trial Submission: Federal Drug Administration (FDA) January 2003 2. 44 Expert Consultant Presentation: Laxdale, Pre-NDA Submission: Federal Drug Administration (FDA). March 2003. 3. 45 Expert Consultant Presentation: Laxdale, New Drug Assessment Committee: European Medicine Agency, December 2003. 4. 4 Consultant, MEDA-Corp, 2003-present 5. 4 Consultant, Amarin Neuroscience, 2004-2005 6. 4 Consultant, Aspreva Pharmaceuticals, 2004-2005 7. 4 Consultant, Migenix - 2005-2007 8. 5 Consultant, Prestwick Pharmaceuticals - 2006-2007 9. Consultant, MethylGene - 2007 10. Consultant, Lundbeck - 2010 11. Member, Advisory Board, Bristol- Myers Squibb, 2011 12. Member, Advisory Board, Isis Pharmaceuticals, 2011 13. Member, Advisory Board, Novartis, 2011 14. Consultant, Teva Pharmaceutical Industries Israel, 2012-present</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Speakers' Bureaus:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Other Activities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Clinical Procedures or Imaging Studies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Commercial Entities:</title>
<list-item>
<p>(1) NeuroSearch Sweden AB HART: A Multi-Centre, Randomized, Double-Blind, Parallel Group Study Comparing Three Doses Of ACR16 Versus Placebo For The Symptomatic Treatment Of Huntington Disease. (2) Medivation, Inc and Pfizer HORIZON: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Safety and Efficacy Study of Dimebon in Patients with Mild-to-Moderate Huntington (3)Medivation Inc and Pfizer HORIZON-PLUS: An Open-label Extension of the HORIZON protocol Evaluating the Safety of dimebon (Latrepirdine) in Subjects with Huntington Disease. (4) NeuroSeach Sweden AB: OPEN-HART: A Multi-Center, North American Open-Label Extension Study Of Pridopidine (ACR16) In The Symptomatic Treatment Of Huntington Disease.</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Government Entities:</title>
<list-item>
<p>(1) CIHR: In Vivo Studies to define the Role of Progranulin Mutations in Frontotemporal Dementia (2) CIHR: Determination of muscle properties that alter ALS onset and disease progression using the G93A mouse model of ALS</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Academic Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Foundations and Societies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>License Fee Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Royalty Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Research Sponsor:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Legal Proceedings:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tabrizi</surname>
<given-names>Sarah J.</given-names>
</name>
<degrees>FRCP, PhD</degrees>
<author-comment content-type="disclosure">
<p>
<list list-type="order">
<title>Scientific Advisory Boards:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Gifts:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Funding for travel or speaker honoraria:</title>
<list-item>
<p>(1) Huntington's Disease Society of America, Travel and accommodation expenses for invited keynote lecture to patient and family audience</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Editorial Boards:</title>
<list-item>
<p>(1) Journal of Huntington's disease, Member of editorial board, 2012-13 (2) PLoS Currents Huntington's Disease, Member of Editorial Board, 2011-13</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Patents:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Publishing Royalties:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Employment, Commercial Entity:</title>
<list-item>
<p>UCL</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Consultancies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Speakers' Bureaus:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Other Activities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Clinical Procedures or Imaging Studies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Commercial Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Government Entities:</title>
<list-item>
<p>(1) European Union, FP7 Health Call ('Neuromics'), UCL Principal Investigator and coapplicant, 2012-15 (2) Medical Research Council, MR/J003832/1, Principal Applicant, 2012-16 (3) Biotechnology and Biological Sciences Research Council, CASE PhD Studentship, 2011-15 (4) European Union, FP7 Health Call ('PADDINGTON'), UCL Principal Investigator and coapplicant, 2010-13</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Academic Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Foundations and Societies:</title>
<list-item>
<p>(1) European HD Network (2) CHDI Foundation, New York. USA (3) Huntington's Disease Association England & Wales</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>License Fee Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Royalty Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Research Sponsor:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Legal Proceedings:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Roos</surname>
<given-names>Raymund A.C.</given-names>
</name>
<degrees>MD</degrees>
<author-comment content-type="disclosure">
<p>
<list list-type="order">
<title>Scientific Advisory Boards:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Gifts:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Funding for Travel or Speaker Honoraria:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Editorial Boards:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Patents:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Publishing Royalties:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Employment, Commercial Entity:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Consultancies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Speakers' Bureaus:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Other Activities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Clinical Procedures or Imaging Studies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Commercial Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Government Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Academic Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Foundations and Societies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>License Fee Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Royalty Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Research Sponsor:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Legal Proceedings:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Durr</surname>
<given-names>Alexandra</given-names>
</name>
<degrees>MD, PhD</degrees>
<author-comment content-type="disclosure">
<p>
<list list-type="order">
<title>Scientific Advisory Boards:</title>
<list-item>
<p>(1) Pfizer - Genetic Services Advisory Board (2011)</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Gifts:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Funding for Travel or Speaker Honoraria:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Editorial Boards:</title>
<list-item>
<p>(1) Journal of Huntington's Disease (editor); (2) International Advisory Committee for Archives of Neurology (editor)</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Patents:</title>
<list-item>
<p>(1) B 06291873.5 « Anaplerotic therapy of Huntington's disease and other polyglutamine diseases ».</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Publishing Royalties:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Employment, Commercial Entity:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Consultancies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Speakers' Bureaus:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Other Activities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Clinical Procedures or Imaging Studies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Commercial Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Government Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Academic Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Foundations and Societies:</title>
<list-item>
<p>(1) Track HD study, Paris site investigator, 2008-2011</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>License Fee Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Royalty Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Research Sponsor:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Legal Proceedings:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Becker</surname>
<given-names>Chris</given-names>
</name>
<degrees>PhD</degrees>
<author-comment content-type="disclosure">
<p>
<list list-type="order">
<title>Scientific Advisory Boards:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Gifts:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Funding for Travel or Speaker Honoraria:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Editorial Boards:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Patents:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Publishing Royalties:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Employment, Commercial Entity:</title>
<list-item>
<p>Protein Metrics Inc., President</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Consultancies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Speakers' Bureaus:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Other Activities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Clinical Procedures or Imaging Studies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Commercial Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Government Entities:</title>
<list-item>
<p>NIH General Medicine, SBIR grant 1R43GM100634-01A1. Role signing authority.</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Academic Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Foundations and Societies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>License Fee Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Royalty Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Research Sponsor:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Legal Proceedings:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sampaio</surname>
<given-names>Cristina</given-names>
</name>
<degrees>MD, PhD</degrees>
<author-comment content-type="disclosure">
<p>
<list list-type="order">
<title>Scientific Advisory Boards:</title>
<list-item>
<p>Scientific Advisory board for Avanir and for Lilly</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Gifts:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Funding for Travel or Speaker Honoraria:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Editorial Boards:</title>
<list-item>
<p>Coordinating Editor of the Movement Disorders CRG, Cochrane Library</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Patents:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Publishing Royalties:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Employment, Commercial Entity:</title>
<list-item>
<p>CHDI Management/CHDI Foundation</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Consultancies:</title>
<list-item>
<p>Alkermes,Otsuka, Lundebeck, Biogen Inc, Takeda,Bia, Avanir, Lilly.</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Speakers' Bureaus:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Other Activities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Clinical Procedures or Imaging Studies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Commercial Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Government Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Academic Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Foundations and Societies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>License Fee Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Royalty Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Research Sponsor:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Legal Proceedings:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tobin</surname>
<given-names>Allan J.</given-names>
</name>
<degrees>PhD</degrees>
<author-comment content-type="disclosure">
<p>
<list list-type="order">
<title>Scientific Advisory Boards:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Gifts:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Funding for Travel or Speaker Honoraria:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Editorial Boards:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Patents:</title>
<list-item>
<p>Use of antibodies to glutamic acid decarboxylase (GAD) to diagnose and predict Type 1 diabetes Use of GAD protein and peptides to prevent or treat Type 1 diabetes</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Publishing Royalties:</title>
<list-item>
<p>Tobin & Dusheck, Asking About Life, 3rd edition, 2004, Brooks Cole Publishing</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Employment, Commercial Entity:</title>
<list-item>
<p>Senior Scientific Advisor, CHDI Foundation, New York NY</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Consultancies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Speakers' Bureaus:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Other Activities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Clinical Procedures or Imaging Studies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Commercial Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Government Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Academic Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Foundations and Societies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>License fee payments, Technology or Inventions:</title>
<list-item>
<p>University of California, royalties on patents listed above on (1) use of antibodies to glutamic acid decarboxylase (GAD) to diagnose and predict Type 1 diabetes, and (2) use of GAD protein and peptides to prevent or treat Type 1 diabetes</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Royalty Payments, Technology or Inventions:</title>
<list-item>
<p>University of California, royalties on patents listed above on (1) use of antibodies to glutamic acid decarboxylase (GAD) to diagnose and predict Type 1 diabetes, and (2) use of GAD protein and peptides to prevent or treat Type 1 diabetes</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Research Sponsor:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Legal Proceedings:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Schulman</surname>
<given-names>Howard</given-names>
</name>
<degrees>PhD</degrees>
<author-comment content-type="disclosure">
<p>
<list list-type="order">
<title>Scientific Advisory Boards:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Gifts:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Funding for Travel or Speaker Honoraria:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Editorial Boards:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Patents:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Publishing Royalties:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Employment, Commercial Entity:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Consultancies:</title>
<list-item>
<p>I was a paid Executive Advisor for Translational Medicine at Caprion Proteomics that conducted the Proteomic analysis</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Speakers' Bureaus:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Other Activities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Clinical Procedures or Imaging Studies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Commercial Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Government Entities:</title>
<list-item>
<p>NINDS/NIMH/NIA. RC2NS069502 PI, 9/2009 to 8/2011</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Academic Entities:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Research Support, Foundations and Societies:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options/Board of Directors Compensation:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>License Fee Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Royalty Payments, Technology or Inventions:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Research Sponsor:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Stock/Stock Options, Medical Equipment & Materials:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
<p>
<list list-type="order">
<title>Legal Proceedings:</title>
<list-item>
<p>NONE</p>
</list-item>
</list>
</p>
</author-comment>
</contrib>
<aff>From CHDI Management/CHDI Foundation (B.B., J.W., C.S.), Princeton, NJ; Centre for Molecular Medicine and Therapeutics (B.R.L.), Department of Medical Genetics, University of British Columbia, Vancouver, Canada; UCL Institute of Neurology (S.J.T.), University College London, Queen Square, London, UK; Department of Neurology (R.A.C.R.), Leiden University Medical Centre, Leiden, the Netherlands; Department of Genetics and Cytogenetics (A.D.), UPMC Université Paris 06, UMR S975 Hôpital de la Salpêtrière, Paris, France; Caprion Proteomics (C.B., H.S.), Menlo Park, CA; and CHDI Management/CHDI Foundation (A.J.T.), Los Angeles, CA. C.B. is currently affiliated with Protein Metrics Inc., San Carlos, CA.</aff>
</contrib-group>
<author-notes>
<corresp>Correspondence to Dr. Borowsky:
<email>beth.borowsky@chdifoundation.org</email>
</corresp>
<fn fn-type="financial-disclosure">
<p>Go to
<ext-link ext-link-type="uri" xlink:href="http://neurology.org/">Neurology.org</ext-link>
for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub">
<day>21</day>
<month>5</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>21</day>
<month>11</month>
<year>2013</year>
</pub-date>
<pmc-comment> PMC Release delay is 6 months and 0 days and was based on the . </pmc-comment>
<volume>80</volume>
<issue>21</issue>
<fpage>1934</fpage>
<lpage>1941</lpage>
<history>
<date date-type="received">
<day>10</day>
<month>7</month>
<year>2012</year>
</date>
<date date-type="accepted">
<day>06</day>
<month>2</month>
<year>2013</year>
</date>
</history>
<permissions>
<copyright-statement>© 2013 American Academy of Neurology</copyright-statement>
<copyright-year>2013</copyright-year>
<copyright-holder>American Academy of Neurology</copyright-holder>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="WNL205050.pdf"></self-uri>
<abstract>
<sec>
<title>Objective:</title>
<p>To evaluate plasma 8-hydroxy-deoxy-guanosine (8OHdG) levels as a potential biomarker of premanifest and early Huntington disease (HD).</p>
</sec>
<sec>
<title>Methods:</title>
<p>Personnel from 2 independent laboratories quantified 8OHdG in blinded longitudinal plasma samples taken 24 months apart from 160 TRACK-HD participants, as well as samples containing control plasma with added (“spiked”) 8OHdG. One laboratory used a liquid chromatography–electrochemical array (LCECA) assay, and the other used liquid chromatography–mass spectrometry (LCMS).</p>
</sec>
<sec>
<title>Results:</title>
<p>The LCMS assay was more accurate than the LCECA assay for measurements of “spiked” 8OHdG levels in plasma. Neither assay demonstrated cross-sectional differences in plasma 8OHdG among controls, premanifest HD, and early symptomatic HD. Similarly, neither assay showed longitudinal changes in any disease group over 24 months.</p>
</sec>
<sec>
<title>Conclusions:</title>
<p>Plasma concentration of 8OHdG is not a biomarker of disease state or progression in HD. We recommend that future putative biomarker studies use blinded sample analysis, standard curves, independent analytical methods, and strict quality control of sample collection and storage.</p>
</sec>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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