The identification of biomarkers specific to a particular disease provides a means to better diagnose the disease condition and aids in the design and testing of drugs in clinical trials. Biomarkers specific to amyotrophic lateral sclerosis (ALS) remain unknown, thus limiting our ability to provide a more rapid disease diagnosis. In addition, the lack of ALS specific biomarkers necessitates the use of clinical assessments such as muscle strength indicators and respiratory function measurements to test potential drug benefits in clinical trials of ALS patients. Such measurements may be poor outcome determinants to identify individual drugs that may have limited but positive affects, thereby greatly limiting our ability to identify the best drug combination for maximal patient benefit. Our proposed study will identify ALS specific biomarkers from the cerebral spinal fluid. We hypothesize that a proteomic analysis of cerebral spinal fluid (CSF) from ALS patients and control subjects will identify quantitative and qualitative disease-associated protein changes.
Our specific aim i s to utilize mass spectrometry based proteomic techniques to identify specific protein biomarkers that occur in ALS patients, thus identifying a novel biomarker signature for ALS. A panel of ALS specific biomarkers is critical for early disease detection and more efficient clinical trials. Our preliminary findings demonstrate the ability to identify mass spectral peaks in the CSF that are diagnostic for ALS. We have identified a panel of 13 putative ALS specific biomarkers. Our proposed studies will both further characterize these putative biomarkers and examine alterations in the proteomic biomarker signature pattern of ALS during disease progression. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21ES013469-02
Application #
6893439
Study Section
Special Emphasis Panel (ZNS1-SRB-E (06))
Program Officer
Kirshner, Annette G
Project Start
2004-05-07
Project End
2007-10-31
Budget Start
2005-05-01
Budget End
2007-10-31
Support Year
2
Fiscal Year
2005
Total Cost
$222,750
Indirect Cost
Name
University of Pittsburgh
Department
Pathology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Ryberg, Henrik; An, Jiyan; Darko, Samuel et al. (2010) Discovery and verification of amyotrophic lateral sclerosis biomarkers by proteomics. Muscle Nerve 42:104-11
Bowser, Robert; Lacomis, David (2009) Applying proteomics to the diagnosis and treatment of ALS and related diseases. Muscle Nerve 40:753-62
Ranganathan, Srikanth; Nicholl, Georgina C B; Henry, Sarah et al. (2007) Comparative proteomic profiling of cerebrospinal fluid between living and post mortem ALS and control subjects. Amyotroph Lateral Scler 8:373-9
Kolarcik, Christi; Bowser, Robert (2006) Plasma and cerebrospinal fluid-based protein biomarkers for motor neuron disease. Mol Diagn Ther 10:281-92
Ranganathan, Srikanth; Williams, Eric; Ganchev, Philip et al. (2005) Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis. J Neurochem 95:1461-71