Editing Biomarkers



''A diagnostic biomarker for ALS would permit early intervention with disease-modifying therapies while a biomarker for disease activity could accelerate the pace of drug discovery by facilitating shorter, and less costly, drug trials to be conducted with a smaller number of patients. Neurofilaments are the most abundant neuronal cytoskeletal protein. We set out to determine whether pNfH was a credible biomarker for ALS. pNfH levels were determined using an ELISA for 150 ALS subjects and 140 controls. We demonstrated a seven-fold elevation in the cerebrospinal fluid (CSF) levels of phosphorylated neurofilament heavy subunit (pNfH) in ALS (median = 2787 pg/ml, n = 150), compared to headache and other benign controls (394 pg/ml, n = 100, p = < 0.05). There was a 10-fold elevation of pNfH compared to ALS mimics (266 pg/ml, n = 20) and other neurodegenerative and inflammatory conditions (279 pg/ml for n = 20) which was also highly significant (p = < 0.05). pNfH achieved a diagnostic sensitivity of 90% and specificity of 87% in distinguishing ALS from all controls. We also detected an inverse correlation between CSF pNfH levels and disease duration (time from symptom onset to death, r(2 = )0.1247, p = 0.001). In conclusion, pNfH represents a promising candidate for inclusion in a panel of diagnostic and prognostic biomarkers.'' {{#pmid:23134506|ganesalingam2013}}


== References ==


[[Category:Key concepts]]
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−	''The diagnosis is mainly based on clinical symptoms and there is a need for ALS-specific biomarkers to make an early and precise diagnosis, for development of disease-modifying drugs and to gain new insights into pathophysiology. Areas covered: In the present review, we summarize studies using mass spectrometric (MS) approaches to identify protein alterations in the cerebrospinal fluid (CSF) of ALS patients. In total, we identified 11 studies fulfilling our criteria by searching in the PubMed database using the keywords "ALS" and "CSF" combined with "proteome", "proteomic", "mass spectrometry" or "protein biomarker". Ten proteins were differently regulated in ALS CSF compared to controls in at least 2 studies. We will discuss the relevance of the identified proteins regarding the frequency of identification, extent of alteration and brain-specificity. Expert commentary: Most of the identified CSF biomarker candidates are irreproducible or mainly blood-derived. We assign the missing success of CSF proteomic studies in biomarker discovery to a lack of sensitivity, unsuitable normalization, low quality assurance and variations originating from sample preparation. These issues must be improved in future proteomic studies in CSF.'' {{#pmid:28799854\|barschke2017}}	+

	''A diagnostic biomarker for ALS would permit early intervention with disease-modifying therapies while a biomarker for disease activity could accelerate the pace of drug discovery by facilitating shorter, and less costly, drug trials to be conducted with a smaller number of patients. Neurofilaments are the most abundant neuronal cytoskeletal protein. We set out to determine whether pNfH was a credible biomarker for ALS. pNfH levels were determined using an ELISA for 150 ALS subjects and 140 controls. We demonstrated a seven-fold elevation in the cerebrospinal fluid (CSF) levels of phosphorylated neurofilament heavy subunit (pNfH) in ALS (median = 2787 pg/ml, n = 150), compared to headache and other benign controls (394 pg/ml, n = 100, p = < 0.05). There was a 10-fold elevation of pNfH compared to ALS mimics (266 pg/ml, n = 20) and other neurodegenerative and inflammatory conditions (279 pg/ml for n = 20) which was also highly significant (p = < 0.05). pNfH achieved a diagnostic sensitivity of 90% and specificity of 87% in distinguishing ALS from all controls. We also detected an inverse correlation between CSF pNfH levels and disease duration (time from symptom onset to death, r(2 = )0.1247, p = 0.001). In conclusion, pNfH represents a promising candidate for inclusion in a panel of diagnostic and prognostic biomarkers.'' {{#pmid:23134506\|ganesalingam2013}}		''A diagnostic biomarker for ALS would permit early intervention with disease-modifying therapies while a biomarker for disease activity could accelerate the pace of drug discovery by facilitating shorter, and less costly, drug trials to be conducted with a smaller number of patients. Neurofilaments are the most abundant neuronal cytoskeletal protein. We set out to determine whether pNfH was a credible biomarker for ALS. pNfH levels were determined using an ELISA for 150 ALS subjects and 140 controls. We demonstrated a seven-fold elevation in the cerebrospinal fluid (CSF) levels of phosphorylated neurofilament heavy subunit (pNfH) in ALS (median = 2787 pg/ml, n = 150), compared to headache and other benign controls (394 pg/ml, n = 100, p = < 0.05). There was a 10-fold elevation of pNfH compared to ALS mimics (266 pg/ml, n = 20) and other neurodegenerative and inflammatory conditions (279 pg/ml for n = 20) which was also highly significant (p = < 0.05). pNfH achieved a diagnostic sensitivity of 90% and specificity of 87% in distinguishing ALS from all controls. We also detected an inverse correlation between CSF pNfH levels and disease duration (time from symptom onset to death, r(2 = )0.1247, p = 0.001). In conclusion, pNfH represents a promising candidate for inclusion in a panel of diagnostic and prognostic biomarkers.'' {{#pmid:23134506\|ganesalingam2013}}