Early detection of Amyotrophic Lateral Sclerosis utilizing

Proteomic and Metabolomic to identify biomarkers

Juan Carlos Torres Sánchez

BIOL 3095

Introduction

• Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that affects the motor neurons.

• Has no cure.

• Third commonest neurodegenerative disease after Alzheimer and Parkinson disease

• Riluzole

introduction

• Metabolomics and Proteomics

•Techniques

biomarkers

http://www.genenews.com/node/35

biomarkers

•Increasing in use in early diagnosis of diseases.

•Monitor disease progression.

•Scientists are trying to find biomarkers.

•Cerebrospinal fluid (CSF) or plasma

proteomics

•Encompasses the study of expressed proteins.

•Proteomics analyses have been used to uncover biomarkers in many other diseases.

(Wright and Semmes 2003)

Proteomics Investigation

• Robert Bowser used proteomic profile of CSF from recently diagnosed ALS patients and control subjects

• Three biomarkers were identified in ALS patients

• transthyretin

• cystatin C

• carboxy-terminal fragment of neuroendocrine protein 7B2

(Ranganathan et.al. 2005)

proteomics

• Cystatin C • gained interest as a candidate

diagnostic biomarker for ALS

• Plasma cystatin C • extensively characterized as a

biomarker for kidney function

(Wilson et.al. 2010)

metabolomics

• Newborn cousin to genomics and proteomics.

• Increasingly being used in a variety of health applications.

• A growing field.

• NMR (nuclear magnetic resonance)

metabolomics

•Metabolomic studies have been performed via different analytical methods.

•NMR appears to be cost-effective, useful in routine care, and screening.

•The highest yield of biomarkers is found in CSF.

Metabolomics investigation

• A research done by Christian R. Andres and colleagues

• 17 metabolites

• CSF screening by NMR could be a useful, simple and low cost tool to improve the early diagnosis of ALS.

• Perturbation of glucose metabolism, and the need to further explore cerebral energetic metabolism.

(Blasco et.al. 2010)

conclusion

• Amyotrophic lateral sclerosis is a disease that affects a small portion of the population of the United States.

• Proteomics and Metabolomics are new studies that can be applied for an early detection of amyotrophic lateral sclerosis.

• The advances are great, but there is still progress to be made, the results in those studies have still brought the need to go through validation.

• Both of these studies have more pros than cons

conclusion

• Proteomics and Metabolomics have helped in other type of diseases.

• They have been recently helpful in the area of cancer for early prognosis.

• In conclusion, additional studies need to be conducted.

references

• Blasco H, Corcia P, Moreau C, Veau S, Fournier C, Vourc’h P, Emond Patrick, Gordon P, Pradat PF, Praline J, Devos D, Desbarats L and Andres CR. 2010. H-NMR-Based Metabolomic Profiling of CSF in Early Amyotrophic Lateral Sclerosis. Plos One. 5(10):e13223

• Gordon P. Amyotrophic Lateral Sclerosis: Pathophysiology, Diagnosis and Management. 2011. CNS Drugs. 25(1):1-16

• Ranganathan S, Williams E, Ganchev P, Gopalakrishnan V, Lacomis D, Urbinelli à L, Newhall K, Cudkowicz ME, Brown Jr. RH and Bowser R. 2005. Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis. Journal of Neurochemestry. 95:1461–1471

• Süssmuth S, Brettschneider J, Ludolph A and Tumani Hayrettin. Biochemical Markers in CSF of ALS Patients. 2008. Current Medical Chemistry. 15:1788-1801

• Tyagi S, Raghvendra, Singh U, Kalra T and Munjal K. Applications of metabolomics - a systematic study of the unique chemical fingerprints: an overview. 2010. International Journal of Pharmaceutical Sciences Review and Research. 3(1):83-86

references

• Wilson ME, Boumaza I, Lacomis D and Bowser R. Cystatin C: A Candidate Biomarker for Amyotrophic Lateral Sclerosis. 2010. Plos One. 5(12):e15133.

• Wright G and Semmes O. Proteomics in Health and Disease. 2003. Journal of Biomedicine and Biotechnology. 4:215-216

• Wuolikainen A, Moritz T, Marklund SL, Antti H, Munch P. Disease-Related Changes in the Cerebrospinal Fluid Metabolome in Amyotrophic Lateral Sclerosis Detected by GC/TOFMS. 2011. Plos One. 6(4):e17947

• Wuolikainen A, Hedenstro M, Moritz T, Marklund SL, Antti H and Andersen PM. Optimization of procedures for collecting and storing of CSF for studying the metabolome in ALS. 2009. The World Federation Of Neurology Research Group On Motor Neuron Diseases. 10(4):229-236