Chitinase proteins in neurologic disease

Patent metadata

Field	Value
Publication number	US-12050217-B2
Application number	US-202117157387-A
Country	US
Kind code	B2
Filing date	Jan 25, 2021
Priority date	Jan 24, 2020
Publication date	Jul 30, 2024
Grant date	Jul 30, 2024

Abstract

The present disclosure describes methods of determining a treatment protocol for and/or a prognosis for a subject suspected of or at risk of suffering from a neurologic disease or disorder, including such diseases and disorders that involve motor neuron function such as ALS. The methods comprise detecting the presence of a chitinase protein in a biological sample.

First claim

What is claimed is:

1. A method of categorizing a human subject for treatment, wherein the subject is suspected of having or is at risk of having amyotrophic lateral sclerosis (ALS), the method comprising:
a) determining a CHI3L1 protein optimal cutoff concentration and a Chit-1 protein optimal cutoff concentration for categorizing a subject as having ALS, wherein determining the CHI3L1 optimal cutoff concentration and the Chit-1 optimal cutoff concentration comprises:
(i) obtaining CHI3L1 and Chit-1 protein concentrations measured in cerebrospinal fluid (CSF) samples obtained from subjects having ALS and CSF samples from control subjects;
(ii) obtaining a first receiver operating characteristic (ROC) curve using the CHI3L1 protein concentrations of (i) and a second ROC curve using the Chit-1 protein concentrations of (i) by applying a statistical modeling technique;
(iii) calculating a first Youden index for each point of the first ROC curve corresponding to a concentration of CHI3L1 between 6 ng and 7 ng/mL and calculating a second Youden index for each point of the second ROC curve corresponding to a Chit-1 concentration between 275 ng/ml and 285 ng/ml; and
(iv) identifying a first highest calculated Youden index from the first Youden index from (iii) and a second highest calculated Youden index from the second Youden index from (iii), wherein the first highest calculated Youden index represents the CHI3L1 optimal cutoff concentration and the second highest calculated Youden index represents the Chit-1 optimal cutoff concentration;

b) performing an immunoassay to determine a concentration of the CHI3L1 protein and a concentration of the Chit-1 protein in a CSF sample obtained from the subject;
c) comparing the concentration of the CHI3L1 protein in the CSF sample to the CHI3L1 optimal cutoff concentration determined in step (a) and comparing the concentration of the Chit-1 protein in the CSF sample to the Chit-1 optimal cutoff concentration determined in step (a);
d) categorizing the subject as having ALS if the concentration of the CHI3L1 protein in the CSF sample is equal to or higher than the CHI3L1 optimal cutoff concentration and if the concentration of the Chit-1 protein in the CSF sample is equal to or higher than the Chit-1 optimal cutoff concentration, wherein accuracy of categorization of a subject as having ALS is improved by comparing in combination the concentration of the CHI3L1 protein to the CHI3L1 optimal cutoff concentration and comparing the concentration of the Chit-1 protein to the Chit-1 optimal cutoff concentration when compared to categorization of the subject as having ALS by comparing the concentration of the CHI3L1 protein to the CHI3L1 optimal cutoff concentration or comparing the concentration of the Chit-1 protein to the Chit-1 optimal cutoff concentration; and
e) administering an anti-inflammatory agent to the subject when the concentration of the CHI3L1 protein in the CSF sample is equal to or higher than the CHI3L1 optimal cutoff concentration and the concentration of the Chit-1 protein in the CSF sample is equal to or higher than the Chit-1 optimal cutoff.

2. The method of claim 1 , wherein the Chit-1 optimal cutoff concentration further categorizes a subject having ALS as having fast progressing ALS, slow progressing ALS, and healthy subjects.

3. A method of categorizing a human subject for treatment, wherein the subject is suspected of having or is at risk of having amyotrophic lateral sclerosis (ALS), the method comprising:
a) performing an immunoassay to determine a concentration of the CHI3L1 protein and a concentration of the Chit-1 protein in a sample of cerebrospinal fluid (CSF) obtained from the subject;
b) comparing the concentration of the CHI3L1 protein in the CSF sample to a CHI3L1 optimal cutoff concentration of 275 ng/ml to 285 ng/ml and comparing the concentration of the Chit-1 protein in the CSF sample to a Chit-1 optimal cutoff concentration of 6 ng/ml to 7 ng/ml;
c) categorizing the subject as having ALS if the concentration of the CHI3L1 protein in the CSF sample is equal to or higher than the CHI3L1 optimal cutoff concentration and if the concentration of the Chit-1 protein in the CSF sample is equal to or higher than the Chit-1 optimal cutoff concentration; and
d) administering an anti-inflammatory agent to the subject when the concentration of the CHI3L1 protein in the CSF sample is equal to or higher than the CHI3L1 optimal cutoff concentration and the concentration of the Chit-1 protein in the CSF sample is equal to or higher than the Chit-1 optimal cutoff.

Assignees

• Dignity Health

Inventors

• Bowser Robert
• Vu Lucas

Classifications

• C12Y302/01014

  Chitinase (3.2.1.14) · CPC title

• G01N2496/00

  Reference solutions for assays of biological material · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• G01N33/6896

  Neurological disorders, e.g. Alzheimer's disease · CPC title

• G01N33/573 Primary

  for enzymes or isoenzymes · CPC title