Biomarkers for the diagnosis of als
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorRobert P. Bowser
Life of this patent
Estimating the term…
Abstract
Methods for determining the onset of ALS in a subject are provided. One method includes analyzing a sample obtained from the subject for the presence or amount of one or more biomarkers indicative of ALS. In a preferred embodiment, the biomarkers are one or more of the following: C-reactive protein (CRP), cystatin c, plasminogen, complement C3, CysGly-transthyretin, and phosphorylated neurofilament heavy chain (pNFH). The sample is typically cerebral spinal fluid (CSF). The levels or concentrations of the biomarkers can be used to determine the onset of ALS, monitor the progression of ALS, or monitor the progression of a treatment for ALS.
Claims27
A method for selecting a subject for treatment of ALS comprising
- determining the concentration of phosphorylated neurofilament heavy chain (pNFH) in a blood or cerebral spinal fluid sample obtained from the subject;
- determining a ratio of pNFH to complement C3 (C3) in the sample, and
- selecting the subject for treatment if the ratio of pNFH/C3 is greater than 0.000125 and the concentration of pNFH is greater than 0.635 ng/ml.
A method for assisting in diagnosing amyotrophic lateral schlerosis (ALS) in a subject comprising:
- determining the concentration of phosphorylated neurofilament heavy chain (pNFH) in a blood or cerebral spinal fluid sample obtained from the subject,
- determining a ratio of pNFH to complement C3 (C3) in the sample;
- determining the concentration of C Reactive Protein (CRP) in the sample,
- wherein a concentration of pNFH greater than 0.635 ng/ml and a ratio pNFH/C3 greater than 0.000125 and a concentration of CPR greater than 0.3755 is indicative of ALS.
A method for selecting a subject for treatment of ALS comprising:
- determining the concentration of phosphorylated neurofilament heavy chain (pNFH) in a blood or cerebral spinal fluid sample obtained from the subject,
- determining a ratio of pNFH to complement C3 (C3) in the sample;
- determining the concentration of C Reactive Protein (CRP) in the sample,
- selecting the subject for treatment when the concentration of pNFH is greater than 0.635 ng/ml and the ratio pNFH/C3 is greater than 0.000125 and the concentration of CPR is greater than 0.3755 is indicative of ALS.
A method of selecting a subject for treatment for amyotrophic lateral sclerosis (ALS) comprising
- determining pNFH concentration levels in a cerebrospinal fluid sample obtained from the subject;
- and selecting the patient for treatment of ALS if the pNFH concentration is ≧1.366 ng/ml and the subject is female.
A method of selecting a subject for treatment for ALS comprising
- determining pNFH concentration levels and complement C3 concentration levels in a cerebrospinal fluid sample obtained from the subject;
- and selecting the subject for treatment of ALS if the complement C3 level is ≧1.197 and pNFH level is ≧1.366 and the subject is male.
A method of selecting a subject for treatment for ALS comprising
- determining pNFH concentration levels and complement C3 concentration levels in a cerebrospinal fluid sample obtained from the subject;
- and selecting the subject for treatment of ALS if the complement C3 level is between 1.005-4.475, the pNFH level is between 0.645-1.366 and the subject is female.
A method of selecting a subject for treatment for ALS comprising
- determining total cerebrospinal protein concentration and pNFH concentration levels in a cerebrospinal fluid sample obtained from the subject;
- and selecting the subject for treatment of ALS if the total CSF protein concentration is between 569-714 μg/ml and pNFH level is ≧1.366.
A method of selecting a subject for treatment for ALS comprising
- determining pNFH concentration levels, complement C3 concentration levels, and total cerebrospinal protein concentration in a cerebrospinal fluid sample obtained from the subject;
- and selecting the subject for treatment of ALS if the total CSF protein concentration is less than 719 μg/ml, complement C3 is not between 1.005-4.475 and pNFH level is ≧0.645.
A method of selecting a subject for treatment for ALS comprising
- determining pNFH concentration levels and complement C3 concentration levels in a cerebrospinal fluid sample obtained from the subject;
- and selecting the subject for treatment of ALS if the complement C3 level is between 1.005-4.475 and the pNFH level is ≧1.366.
A method of selecting a subject for treatment for ALS comprising
- determining pNFH concentration levels, complement C3 concentration levels, and total cerebrospinal protein concentration in a cerebrospinal fluid sample obtained from the subject;
- and selecting the subject for treatment of ALS if the total CSF protein concentration is less than 719 μg/ml, complement C3 is not between 1.005-4.475 μg/ml and pNFH level is ≧0.645 ng/ml.
A method of selecting a subject for treatment for ALS comprising
- determining pNFH concentration levels, complement C3 concentration levels, and total cerebrospinal protein concentration in a cerebrospinal fluid sample obtained from the subject;
- and selecting the subject for treatment of ALS if cystatin C level is ≦2.0 μg/ml and pNFH level is ≧0.75 ng/ml.
A method of selecting a subject for treatment for ALS comprising
- determining pNFH and complement C3 levels;
- and selecting for treatment of ALS if pNFH level is >0.6349 ng/ml AND pNFH/C3 ratio is >0.125.
A computer-implemented method of selecting a subject for treatment of amyotrophic lateral sclerosis (ALS) comprising:
- (i) inputting into a computer expression data for C reactive protein or plasminogen in a cerebral spinal fluid sample obtained from the subject;
- and
- (ii) comparing the expression data to predetermined expression data for C reactive protein or plasminogen from subjects without amyotrophic lateral sclerosis;
- and
- (iii) selecting the subject wherein the expression data of C reactive protein or plasminogen in the cerebral spinal fluid sample obtained from the subject is correlated by the computer system to be indicative of ALS.
A method for assessing survivability of an ALS subject comprising quantifying the levels of cystatin C in a sample obtained from the ALS subject wherein increased levels of cystatin C in the sample is indicative of increased survivability compared to ALS subjects having lower levels of cystatin C, wherein the ALS is limb onset ALS.
A method for assisting in diagnosing amyotrophic lateral schlerosis (ALS) in a subject comprising:
- determining the concentration of phosphorylated neurofilament heavy chain (pNFH) in a blood or cerebral spinal fluid sample obtained from the subject, wherein a concentration greater than 0.635 ng/ml is indicative of ALS.
A method for assisting in diagnosing amyotrophic lateral schlerosis (ALS) in a subject comprising:
- determining a ratio of pNFH to complement C3 (C3) in a blood or cerebral spinal fluid sample obtained from the subject, wherein a ratio greater than 0.000125 is indicative of ALS.
A method for assessing the efficacy of a treatment for ALS comprising
- administering a drug to a subject having ALS,
- determining the concentration of pNFH in a blood or cerebrospinal fluid sample obtained from the subject before and after administration of the drug;
- wherein the treatment is effective if levels of pNFH decrease after administration of the drug relative to levels of pNFH prior to administration of the drug.
A method for assisting in the diagnosis of ALS comprising
- applying any one of the rules listed in Table 4.
A method of determining survivability in a subject having ALS comprising
- determining the concentration of cystatin C in a sample obtained from the subject, wherein a concentration of cystatin C lower than 2.75 μg/ml indicates a decreased survivability compared to ALS subjects having greater than 2.75 μg/ml of cystatin.
Dependencies are inferred from the claim text.