# US 8,999,655 B2 · Increase of myeloid microvesicles in the cerebrospinal fluid as biomarker of microglia/macrophage activation in neurological disorders

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- Number: US 8,999,655 B2
- Document ID: US8999655B2
- Status: Granted
- Kind: B2
- Application number: 13/581,646
- Filed: 2011-03-03
- Published: 2013-02-14
- Granted: 2015-04-07
- Earliest claimed: 2010-03-03
- Assignees: Consiglio Nazionale Delle Ricerche; Universita' Degli Studi Di Milano; Ospedale San Raffaele S.R.L.
- Applicants: Claudia Verderio; Michela Matteoli; Roberto Furlan
- Inventors: Claudia Verderio; Michela Matteoli; Roberto Furlan
- Web page: https://patentgrep.com/patent/US8999655B2

## CPC

- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- G01N 33/5076: {involving cell organelles, e.g. Golgi complex, endoplasmic reticulum}
- G01N 33/5091: {for testing the pathological state of an organism}
- G01N 2800/28: Neurological disorders
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- G01N 2800/56: Staging of a disease; Further complications associated with the disease
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention relates to a method for the diagnostic and/or prognostic of a neurological disease characterized by an inflammation process in a subject comprising measuring the amount of myeloid derived microvesicles in a cerebrospinal fluid sample obtained from the subject. The invention further relates to a method for predicting and/or monitoring the efficacy of a treatment for a neurological pathology or for monitoring a neurological disease progression.

## Claims

### Claim 1

A method for diagnosing and/or monitoring of a neurological disease characterized by an inflammatory process wherein the neurological disease and/or the inflammatory process is characterized by microglial activation in a subject, the method comprising
(a) labeling microglia/macrophage derived microvesicles with IB-4, wherein the microvesicles are present in a cerebrospinal fluid sample obtained from the subject;
(b) measuring the amount of said labelled myeloid microglia/macrophage derived microvesicles in said sample obtained from the subject,
wherein if the measured amount is above a control value, the subject is affected by a neurological disease characterized by an inflammatory process.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the microglia/macrophage derived microvesicles are further positive for a marker selected from the group consisting of Iba-1, OX42 and CD11b.

### Claim 3 (depends on 1)

The method according to claim 1 wherein the amount of the microglia/macrophage derived microvesicles is measured by means of flow cytometry technology.

### Claim 4 (depends on 1)

The method according to claim 1 wherein the amount of the microglia/macrophage derived microvesicles is measured by means of immunogold electron microscopy.

### Claim 5 (depends on 1)

The method according to claim 1 wherein the control value is between 1.5 to 2 microvesicles/μl.

### Claim 6

A method for predicting and/or monitoring the efficacy of a treatment or progression of a neurological disease, wherein the neurological disease is characterized by an inflammatory process in a subject, comprising:
(a) labeling microglia/macrophage derived microvesicles with IB-4, wherein the microvesicles are present in a cerebrospinal fluid sample obtained from the subject,
(b) measuring the amount of the labeled microglia/macrophage derived microvesicles in a cerebrospinal fluid sample obtained from the subject, and
(c) comparing the measured amount to a control value.

### Claim 7 (depends on 6)

The method according to claim 6 wherein the neurological disease is characterized by an inflammatory process.

### Claim 8 (depends on 7)

The method according to claim 7 wherein the neurological disease and/or the inflammatory process is characterized by microglial activation.

### Claim 9 (depends on 6)

The method according to claim 6 wherein the neurological disease is selected from the group consisting of Multiple sclerosis, Alzheimer's disease, clinically isolated syndrome (CIS), Guillain-Barré Syndrome (GBS), neuromyelitis optica (NMO), chronic inflammatory demyelinating polyneuropathy (CIDP), frontotemporal dementia, radiculitis, encephalitis and meningoencephalitis.

### Claim 10 (depends on 6)

The method according to claim 6, wherein the microglia/macrophage derived microvesicles are further positive for a marker selected from the group consisting of Iba-1, and OX42.

### Claim 11 (depends on 6)

The method according to claim 6, wherein the amount of the microglia/macrophage derived microvesicles is measured by means of flow cytometry technology.

### Claim 12 (depends on 6)

The method according to claim 6, wherein the amount of the microglia/macrophage derived microvesicles is measured by means of immunogold electron microscopy.