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Metabonomics

WDA 2010 . Metabonomics. A New Potential Diagnostic Tool. David Huffman Western Michigan University. Current Challenges. Difficulty in diagnosis Symptoms not always specific Confusion with other disorders Speed of diagnosis To minimize complications Monitoring treatment regimen

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Metabonomics

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  1. WDA 2010 Metabonomics A New Potential Diagnostic Tool David Huffman Western Michigan University

  2. Current Challenges • Difficulty in diagnosis • Symptoms not always specific • Confusion with other disorders • Speed of diagnosis • To minimize complications • Monitoring treatment regimen • Short and long term effects Ala et al. Lancet 2007, 369, 397

  3. http://www.nytimes.com/2009/08/18/health/18tran.html

  4. Goals • Early diagnosis when clinical manifestions are mild • Predict neurological and liver function changes Metabonomics

  5. Definition of terms METABOLITE is a small molecule whose concentration changes as a function of something; usually not a protein or enzyme METABOLOME is the repetoire of biochemicals present in cells, tissue, and body fluids An example would be blood glucose Metabonomics

  6. Definition of terms METABOLOMICS is the global analysis of the type and quantity of all metabolites in biological fluids or tissue METABONOMICS is the study of metabolic responses to pathophysiological stimuli Metabonomics

  7. Metabonomics “The relevance of metabonomics could be greatly enhanced if it were possible to identify an invariant part of the individual metabolome of a ‘healthy’ subject with respect to, for example, pathological states, in such a way as to perform prediction, early diagnosis and prognosis of pathologies.” Assfalg et al. Proc NatlAcadSci 2008, 105, 1420

  8. Metabonomics “. . . traditional biomedical/clinical approaches are limited by the number of parameters as well as in their efficiency, and they provide only a fragmented perspective on the health status of an individual.” Assfalg et al. Proc NatlAcadSci 2008, 105, 1420

  9. Current Biochemical TestsFor WD Typically don’t measure small metabolites • AST and ALT (Aminotransferases) • ALP (AlkPhosphatase) • Bilirubin, Albumin • INR, CBC • Serum Ceruloplasmin Roberts & SchilskyHepatology 2003, 37, 1475

  10. Current Testing Methods “However, most clinical chemistry tests available today rely on old technologies that only measure a single chemical in blood, urine or other biofluid, and these tests are generally neither sensitive nor specific for any one particular disease. Comprehensive chemical analyses of urine or blood have simply never been done in a clinical setting before. ” Slupsky, Biomarkers Med. 2010, 4, 195

  11. Prospect of Metabonomics • Measure a number of different metabolites simultaneously • Obtain a unique fingerprint of a individual in metabolic space and time • Develop new markers for WD diagnosis and monitoring Metabonomics

  12. Metabolites Monitored • amino acids • amines • lipids • sugars and derivatives • nucleic acids • other metabolic intermediates Metabonomics

  13. Metabonomic Phenotypes NMR Fingerprint from one individual*,‡ Multivariate Analysis of 21 Individuals *not actual data ‡urine has over 2500 different metabolites at >1 mM Assfalg et al. Proc NatlAcadSci 2008, 105, 1420

  14. Metabotypes genes lifestyle etc. • The metabotype consists of a variable part (environment) and an invariant part (genetics + environment) • The invariant part persists for at least two-three years • The discovery of the existence of individual metabotypes has a strong biomedical potential Bernini, P.; Bertini, I.; Luchinat, C.; Nepi, S.; Saccenti, E.; Schäfer, H.; Schütz, B.; Spraul, M.; Tenori, L. Individual human phenotypes in metabolic space and time, J. Prot. Res. 2009

  15. CeliacDiseaseMetabonomics After gluten-free diet the metabolic fingerprint reverts to normal Bertini, I.; Calabrò, A.; De Carli, V.; Luchinat, C.; Nepi, S.; Porfirio, B.; Renzi, D.; Saccenti, E.; Tenori, L.The metabonomic signature of celiac disease, J. Proteome Res. 2009,8(1), 170

  16. Metabonomic Applications • New Markers for Disease • Facilitate rapid diagnosis • Monitor Maintenance Therapy • Pre/Post Drug Treatment • Pre/Post Surgery • Establish Parameters to Monitor Health • Routine Multivariate Analysis of body fluid or tissue Metabonomics

  17. The Next Step • Establish a metabonomics study of WD patients Metabonomics

  18. Current Funding National Science Foundation Metabonomics

  19. Collaborators: IvanoBertini Claudio Luchinat

  20. Huffman Group Summer 2010

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