Lysosomal storage disorder biomarkers and methods of use thereof

A technology of lysosomal storage disease and biomarker, applied in the direction of biochemical equipment and methods, biological testing, chemical instruments and methods, etc.

Pending Publication Date: 2021-12-21
DENALI THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although much research has been done to investigate the underlying molecular mechanisms of LSD and develop new treatments, additional work is needed

Method used

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  • Lysosomal storage disorder biomarkers and methods of use thereof
  • Lysosomal storage disorder biomarkers and methods of use thereof
  • Lysosomal storage disorder biomarkers and methods of use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach 1

[0474] Embodiment 1. A method of detecting one or more biomarkers in a subject with a lysosomal storage disorder (LSD), the method comprising:

[0475] 1) measuring the concentration of a combination of two or more lipids in a sample from said subject, wherein said combination of lipids is selected from the group consisting of:

[0476] a) bis(monoacylglycerol) phosphate (BMP);

[0477] b) GM2 gangliosides and / or GM3 gangliosides;

[0478] c) GD3 ganglioside;

[0479] d) GD1a / b gangliosides; and

[0480] e) Glucosylceramide (GlcCer);

[0481]2) measuring the concentration of GlcCer in a sample from said subject, with the proviso that said LSD is a mucopolysaccharidosis (MPS) condition;

[0482] 3) measuring the concentration of neurofilament light chain (Nf-L) in a sample from said subject; and / or

[0483] 4) measuring the concentration of soluble triggering receptor 2 (sTREM2) expressed on myeloid cells in a sample from said subject.

Embodiment approach 2

[0484] Embodiment 2. A method of assessing the efficacy of a treatment in a subject with LSD, the method comprising:

[0485] 1) measuring the concentration of a combination of two or more lipids in a sample obtained from said subject after administering said treatment, wherein said combination of lipids is selected from the group consisting of:

[0486] a) BMPs;

[0487] b) GM2 gangliosides and / or GM3 gangliosides;

[0488] c) GD3;

[0489] d) GD1a / b; and

[0490] e) GlcCer;

[0491] 2) measuring the concentration of GlcCer in a sample obtained from said subject after administering said treatment, provided that said LSD is an MPS disorder;

[0492] 3) measuring the concentration of Nf-L in a sample obtained from said subject after administration of said treatment; and / or

[0493] 4) measuring the concentration of sTREM2 in a sample obtained from said subject after administration of said treatment;

[0494] Wherein the concentration of the selected lipid / protein in the s...

Embodiment approach 3

[0495] Embodiment 3. A method of identifying a subject with LSD as a candidate for treatment, the method comprising:

[0496] 1) measuring the concentration of a combination of two or more lipids in a sample from said subject, wherein said combination of lipids is selected from the group consisting of:

[0497] a) BMPs;

[0498] b) GM2 gangliosides and / or GM3 gangliosides;

[0499] c) GD3;

[0500] d) GD1a / b; and

[0501] e) GlcCer;

[0502] 2) measuring the concentration of GlcCer in a sample from said subject, with the proviso that said LSD is an MPS disorder;

[0503] 3) measuring the concentration of Nf-L in a sample from said subject; and / or

[0504] 4) measuring the concentration of sTREM2 in a sample from said subject;

[0505] Wherein the concentration of the selected lipid / protein in the sample from the subject is at least as high as the control value, the subject is identified as a candidate for treatment.

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Abstract

Certain embodiments provide a method of detecting one or more biomarkers in a subject having a lysosomal storage disorder, and the method comprises the steps: 1) measuring the concentration of a combination of two or more lipids in a sample from the subject, wherein the combination of lipids is selected from the group consisting of: a) a bis(monoacylglycero)phosphate (BMP); b) a GM2 ganglioside and/or a GM3 ganglioside; c) a GD3 ganglioside; d) a GD1a/b ganglioside; and e) a glucosylceramide (GlcCer); 2) measuring the concentration of GlcCer in a sample from the subject; 3) measuring the concentration of neurofilament light chain (Nf-L) in a sample from the subject; and/or 4) measuring the concentration of soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in a sample from the subject.

Description

[0001] Cross References to Related Applications [0002] This application claims U.S. Provisional Application Serial No. 62 / 777,599 filed December 10, 2018, U.S. Provisional Application Serial No. 62 / 860,039 filed June 11, 2019, U.S. Provisional Application Serial No. 62 / 860,039 filed July 1, 2019 62 / 869,387 and the priority of U.S. Provisional Application Serial No. 62 / 912,253, filed October 8, 2019. The entire contents of the applications cited above are incorporated herein by reference. Background technique [0003] Lysosomal storage disorders (LSDs) are relatively rare inherited metabolic diseases caused by defects in lysosomal function. LSD is usually caused by the deficiency of a single enzyme involved in the breakdown of metabolites in lysosomes. Product buildup due to lack of enzyme activity can affect various organ systems and can lead to severe symptoms and premature death. Most LSDs also have a significant neurologic component, ranging from progressive neurodegen...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68C07K16/28
CPCG01N33/6854C07K2319/30C07K16/2881C07K2317/52C07K16/2803C12Y301/06013A61P43/00A61K2039/505C12N9/16
Inventor A·阿尔圭洛G·阿斯塔里塔A·巴拉J·R·布卢门菲尔德G·迪保罗A·亨利A·A·纽金特J·厄尔曼王军华
Owner DENALI THERAPEUTICS INC
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