Biomarkers of amyotrophic lateral sclerosis and uses thereof
OwnerStanley Hersh APPEL, David Robert BEERS +1inventors
InventorsStanley Hersh APPEL, David Robert BEERS, Howard BERMAN
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to biomarkers and uses thereof in methods for selecting a patient diagnosed with amyotrophic lateral sclerosis (ALS) for an ALS therapy. The present disclosure further relates to methods for identifying the severity of ALS in a patient, treating an ALS patient, and monitoring efficacy of an ALS treatment.
Claims51
A method of treating amyotrophic lateral sclerosis (ALS) comprising:
- (a) collecting a serum sample from a patient diagnosed with ALS before administering a first ALS therapy;
- (b) administering the first ALS therapy to the patient;
- (c) collecting a serum sample from the patient after administering the first ALS therapy;
- (d) measuring concentration of at least one biomarker in the serum samples collected from the patient before and after administering the first ALS therapy, wherein the at least one biomarker is selected from the group consisting of oxidized low-density lipoprotein receptor 1 (OLR1), oxidized low-density lipoprotein (ox-LDL), 4-hydroxynonenal (4-HNE), soluble CD14 (sCD14), lipopolysaccharide binding protein (LBP), C-reactive protein (CRP), interleukin 17F (IL-17F), interleukin 17C (IL-17C), monocyte chemoattractant protein-1 MCP-1 (CCL2), and interleukin-18 (IL-18);
- (e) comparing the concentration of the at least one biomarker in the serum sample collected from the patient after administering the first ALS therapy to a baseline, wherein the concentration of the at least one biomarker in the serum sample collected from the patient before administering the first ALS therapy is the baseline;
- and
- (f) administering a second ALS therapy to the patient if the concentration of at least one biomarker after administering the first ALS therapy is at least one-fold different than the baseline.
A method for selecting a patient for amyotrophic lateral sclerosis (ALS) therapy, the method comprising:
- (a) determining whether a concentration of at least one biomarker in a serum sample collected from a patient diagnosed with or suspected of having ALS is less than, equal to, or greater than, a reference concentration;
- (b) wherein the at least one biomarker is selected from the group consisting of oxidized low-density lipoprotein receptor 1 (OLR1), oxidized low-density lipoprotein (ox-LDL), monocyte chemoattractant protein-1 MCP-1 (CCL2), interleukin-18 (IL-18), and any combination thereof, and.
- (c) selecting the patient for ALS therapy if at least one biomarker is equal to or less than the reference concentration.
A kit for detecting and quantifying the level of one or more ALS biomarkers in a serum sample obtained from a patient having or suspected of having ALS, wherein the ALS biomarkers are selected from the group consisting of oxidized low-density lipoprotein receptor 1 (OLR1), oxidized low-density lipoprotein (ox-LDL), monocyte chemoattractant protein-1 MCP-1 (CCL2), interleukin-18 (IL-18), and any combination thereof.
A method of treating treatment-responsive ALS, comprising administering to a patient diagnosed with treatment-responsive ALS a therapeutically effective amount of an ALS therapy, wherein the treatment-responsive ALS is characterized as having at least one biomarker equal to or less than a reference concentration,
- wherein the at least one biomarker is selected from the group consisting of oxidized low-density lipoprotein receptor 1 (OLR1), oxidized low-density lipoprotein (ox-LDL), monocyte chemoattractant protein-1 MCP-1 (CCL2), and interleukin-18 (IL-18);
- and,
- wherein the reference concentration is an average concentration of the biomarker measured in serum samples collected from at least 10 healthy subjects having the same age, gender, and/or ethnicity as the patient.
A method of determining whether a patient diagnosed with ALS is indicated as likely to be responsive to ALS treatment, comprising detecting the concentration of at least one biomarker compared to a reference concentration in a serum sample collected from the patient, wherein the at least one biomarker having a concentration equal to or less than the reference concentration indicates that the patient is likely to be responsive to ALS treatment,
- wherein the at least one biomarker is selected from the group consisting of oxidized low-density lipoprotein receptor 1 (OLR1), oxidized low-density lipoprotein (ox-LDL), monocyte chemoattractant protein-1 MCP-1 (CCL2), and interleukin-18 (IL-18);
- and,
- wherein the reference concentration is an average concentration of the biomarker measured in serum samples collected from at least 10 healthy subjects having the same age, gender, and/or ethnicity as the patient.
Dependencies are inferred from the claim text.