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Juan carlos ppt als
1. Early detection of Amyotrophic Lateral
Sclerosis utilizing Proteomic and
Metabolomic to identify biomarkers
Juan Carlos Torres Sánchez
BIOL 3095
2. 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
5. biomarkers
• Increasing in use in early diagnosis of
diseases.
• Monitor disease progression.
• Scientists are trying to find biomarkers.
• Cerebrospinal fluid (CSF) or plasma
6. proteomics
• Encompasses the study of expressed
proteins.
• Proteomics analyses have been used
to uncover biomarkers in many other
diseases.
(Wright and Semmes 2003)
7. 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)
8. 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)
9. metabolomics
• Newborn cousin to genomics and
proteomics.
• Increasingly being used in a variety of health
applications.
• A growing field.
• NMR (nuclear magnetic resonance)
10. 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.
11. 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.
12. 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
13. 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.
14. 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
15. 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
Editor's Notes
(2)Treatments are beingmadethatexpandthelifeexpectancy. (4)Itistheonly FDA approveddrugtotreatthisdisease, butitonlyextendsthelifeexpectancybytwotothreemonths.
Two fields of science that are studying specific biomarkers for early diagnosis in ALS are Proteomics and Metabolomics, with progress in finding biomarkers for ALS. They use differenttechniquesfortheidentification of biomarkersfor ALS
These are the questions that most scientist need to ask to see if that specific biomarker is usefull.
(2) would aid in the design and execution of human clinical trials, also to provide novel targets for future drug therapies(3)that could help in the early diagnosis and prognosis of ALS, and for the utilization in routine patient checkup.(4)These are werethecollectionsamplesformostbiomarkers are takenfor ALS.
-using a type of mass spectometry technique -transthyretin and cystatin C were found in less amounts, while protein 7B2 was in more amounts in comparison with normal patients without ALS.
has recently gained interest as a candidate diagnostic biomarker for ALS; further studies are required to fully characterize its biomarker utility.(2)has been extensively characterized as a biomarker for kidney function, also as a prognostic indicator of the risk of morbidity andmortality relating to cardiovascular disease.
(1) Specifically, metabolomics involves the rapid, high throughput characterization of the small molecule metabolites found in an organism.(2 )including pharmacology, pre-clinical drug trials, toxicology, transplant monitoring, newborn screening and clinical chemistry. (3) detects and quantifies the low molecular weight molecules, known as metabolites, produced by active, living cells under different conditions and times in their life cycles (4) is playing an important role in metabolomics because of its ability to observe mixtures of small molecules in living cells or in cell extracts
(1)such as high performance liquid chromatography followed by electrochemical detection or high-resolution 1H NMR spectroscopy. (3)Different kinds of biological fluids have been screened, but CSF may have the highest yield of biomarkers in ALS because of its direct contact with the brain, its accessibility, and its dynamic changes with the cerebral environment
Usedmetabolomicstoidentifyspecificbiomarkers(3) The conclusion of that study is that (4)The results indicate a perturbation of glucose metabolism, and the need to further explore cerebral energetic metabolism.
-A cure for the disease has not been found and the struggle in finding new therapies or techniques that extend the life span of the patient are being looked at. (4) and are an improvement towards finding the cause and a cure, which more scientists should venture.
such as already mentioned multiple sclerosis, schizophrenia, Alzheimer’s disease, and HIV-1 associated cognitive impairment. (3) so that these technics could be performed in the daily patient routine checkup for any disease.