# US 7,611,902 B2 · Diagnostic method for myopathy

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- Number: US 7,611,902 B2
- Document ID: US7611902B2
- Status: Granted
- Kind: B2
- Application number: 11/761,427
- Filed: 2007-06-12
- Published: 2008-01-03
- Granted: 2009-11-03
- Earliest claimed: 2006-06-12
- Assignees: Zora Biosciences Oy
- Inventors: Reijo Laaksonen; Matej Oresic; Terho Lehtimäki; Hannu Päivä
- Web page: https://patentgrep.com/patent/US7611902B2

## CPC

- C12Q 1/6883: for diseases caused by alterations of genetic material
- G01N 33/6893: {related to diseases not provided for elsewhere}
- C12Q 2600/158: Expression markers
- G01N 2800/325: Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
- Y10S 435/975: Kit
- Y10T 436/143333: Saccharide [e.g., DNA, etc.]
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- 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)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

This invention provides a diagnostic method for determining statin induced myopathy. The method is especially applicable for determining warnings, early signs and also symptomatic myopathy. The method includes collecting a lipidomic profile from a biological sample such as blood or serum and comparing the obtained lipidomic profile to reference lipidomic markers. The reference lipidomic markers have been established by combining a pro-inflammatory muscle tissue gene expression profile with a lipidomic profile associated with high dosage statin treatment. This invention also relates to a kit for performing a method for determining statin induced myopathy.

## Claims

### Claim 1

A method for determining statin induced myopathy comprising the steps:
a) providing a biological sample from an individual prior to or during statin treatment,
b) collecting a lipidomic profile from said biological sample,
c) comparing said collected lipidomic profile to reference lipidomic markers, wherein a difference between the collected lipidomic profile and the reference lipidomic markers indicates statin induced myopathy, and said reference lipidomic markers have been established by combining a pro-inflammatory muscle tissue gene expression profile with a lipidomic profile associated with high dosage statin treatment.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the method is for determining a risk of said individual to develop statin induced myopathy.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the method is for determining early warning signs of statin induced myopathy in said individual.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the method is for determining statin induced myopathy in individuals showing symptoms of myopathy.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the proinflammatory muscle tissue gene expression profile is the pathway of arachidonate 5-lipoxygenase activating protein (ALOX5AP) gene.

### Claim 6 (depends on 1)

The method according to claim 1, wherein said reference lipidomic markers are one or more lipid(s) selected from GPCho (0:0/16:0), GPCho (16:0/0:0), GPCho (O-16:2), GPCho (0:0/18:0), GPCho (18:0/0:0), GPCho (0:0/18:1), GPCho (18:1/0:0), GPCho (0:0/18:2), GPCho (18:2/0:0), GPCho(18:3/0:0), GPCho(0:0/20:3), GPCho (20:3/0:0), GPCho(20:4/0:0), GPCho(20:4/0:0), GPCho(22:6/0:0), Cer(d18:1/22:0), DG(36:2), DG(44:12), GPCho(32:0), GPCho (O-32:0), GPCho (32:1), GPCho (O-32:1), GPCho (34:1), GPCho (O-34:1), GPCho (34:2), GPCho (O-34:2), GPCho (34:3), GPCho(O-34:3), GPCho(36:0), GPCho(36:1), GPCho(36:1), GPCho (36:2), GPCho (O-36:2), GPCho (36:3), GPCho (O-36:3), GPCho (O-36:3), GPCho (36:4), GPCho (36:4), GPCho (O-36:4), GPCho (36:5), GPCho (36:5), GPCho (O-36:5), GPCho (38:2), GPCho(38:3), GPCho(38:4), GPCho(38:4), GPCho(38:4), GPCho (O-38:4), GPCho (38:5), GPCho (O-38:5), GPCho (38:6), GPCho(38:6), GPCho(O-38:6), GPCho(38:7), GPCho(O-38:7), GPCho (40:4), GPCho (O-40:4), GPCho (40:6), GPCho (40:7), SM(d18:0/16:0), SM(d18:0/18:0), SMd18:0/24:0), SM(d18:1/16:0), SM (d18:1/16:1), SM (d18:1/18:0), SM (d18:1/18:3), SM(d18:1/20:0), SM(d18:1/22:0), SM(d18:1/22:1), SM(d18:1/24:0), SM(d18:1/24:1), GPEtn(36:1), GPEtn(36:2), GPEtn(38:1), GPEtn(O-38:1), GPEtn(38:2), GPEtn(38:4), GPEtn (O-38:5), GPEtn (O-38:6), GPEtn (40:4), GPEtn (42:6), GPSer(36:0), ChoE(18:0), ChoE(18:1), ChoE(18:2), ChoE(20:4) ChoE(20:5), TG(46:0), TG(46:1), TG(46:2), TG(48:0), TG(48:0), TG(48:1), TG(48:1), TG(48:2), TG(48:3), TG(49:1), TG(50:0), TG(50:0), TG(50:1), TG(50:1), TG(50:2), TG(50:2), TG(50:2), TG(50:3), TG(50:4), TG(51:1), TG(51:2), TG(51:3), TG(52:0), TG(52:1), TG(52:1), TG(52:2), TG(52:2), TG(52:3), TG(52:4), TG(52:5), TG(54:2), TG(54:2), TG(54:3), TG(54:3), TG(54:4), TG(54:4), TG(54:5), TG(54:6), TG(56:5), TG(56:5), TG(56:6), TG(56:7), TG(56:8), TG(56:9), and TG58:8).

### Claim 7 (depends on 1)

The method according to claim 1, wherein said reference lipidomic markers are one or more lipid(s) selected from GPCho(34:3), GPCho(36:0), GPCho(36:3), GPCho(38:2), GPCho(38:3), GPCho(38:4), GPCho(38:5), GPCho(O-38:5), GPCho(38:6), GPCho(38:7), GPCho(O-38:7), GPCho(40:6), SM(d18:0/16:0), SM(d18:0/18:0), SM(d18:1/18:0), SM(d18:1/22:0), GPEtn(38:1), GPEtn(40:4), ChoE(18:0), ChoE(18:2), TG(54:2), TG(54:3), and TG(56:5).

### Claim 8 (depends on 1)

The method according to claim 1, wherein said reference lipidomic markers are established from a lipidomic profile collected from the same individual as the lipidomic profile of (b) is collected and said reference lipidomic markers are established before said individual start statin treatment.

### Claim 9 (depends on 1)

The method according to claim 1, wherein said reference lipidomic marker is established from lipidomic profiles collected from a healthy generalized population.

### Claim 10 (depends on 1)

The method according to claim 1, further comprising:
(d) measuring the expression of the ALOX5AP gene from the biological sample; and
(e) comparing the measured ALOX5AP gene expression to reference ALOX5AP gene expression, wherein a difference between the measured ALOX5AP gene expression and the reference ALOX5AP gene expression indicates statin induced myopathy.

### Claim 11 (depends on 1)

A kit for performing the method according to claim 1, wherein the kit comprises one or more reference lipidomic markers selected from GPCho(0:0/16:0), GPCho (16:0/0:0), GPCho (O-16:2), GPCho (0:0/18:0), GPCho (18:0/0:0), GPCho (0:0/18:1), GPCho (18:1/0:0), GPCho (0:0/18:2), GPCho (18:2/0:0), GPCho (18:3/0:0), GPCho(0:0/20:3), GPCho(20:3/0:0), GPCho(20:4/0:0), GPCho(20:4/0:0), GPCho(22:6/0:0), Cer (d18:1/22:0), DG(36:2), DG (44:12), GPCho (32:0), GPCho (O-32:0), GPCho (32:1), GPCho (O-32:1), GPCho (34:1), GPCho (O-34:1), GPCho (34:2), GPCho (O-34:2), GPCho (34:3), GPCho (O-34:3), GPCho (36:0), GPCho(36:1), GPCho(36:1), GPCho(36:2), GPCho(O-36:2), GPCho(36:3), GPCho(O-36:3), GPCho(O-36:3), GPCho(36:4), GPCho(36:4), GPCho(O-36:4), GPCho(36:5), GPCho(36:5), GPCho(O-36:5), GPCho(38:2), GPCho(38:3), GPCho(38:4), GPCho(38:4), GPCho(38:4), GPCho(O-38:4), GPCho(38:5), GPCho(O-38:5), GPCho(38:6), GPCho(38:6), GPCho(O-38:6), GPCho (38:7), GPCho (O-38:7), GPCho (40:4), GPCho (O-40:4), GPCho (40:6), GPCho (40:7), SM (d18:0/16:0), SM (d18:0/18:0), SMd18:0/24:0), SM(d18:1/16:0), SM(d18:1/16:1), SM(d18:1/18:0), SM (d18:1/18:3), SM (d18:1/20:0), SM (d18:1/22:0), SM(d18:1/22:1), SM(d18:1/24:0), SM(d18:1/24:1), GPEtn (36:1), GPEtn(36:2), GPEtn(38:1), GPEtn(O-38:1), GPEtn(38:2), GPEtn(38:4), GPEtn(O-38:5), GPEtn(O-38:6), GPEtn(40:4), GPEtn(42:6), GPSer(36:0), ChoE(18:0), ChoE(18:1), ChoE(18:2), ChoE(20:4), ChoE(20:5), TG(46:0), TG(46:1), TG(46:2), TG(48:0), TG(48:0), TG(48:1), TG(48:1), TG(48:2), TG(48:3), TG(49:1), TG(50:0), TG(50:0), TG(50:1), TG(50:1), TG(50:2), TG(50:2), TG(50:2), TG(50:3), TG(50:4), TG(51:1), TG(51:2), TG(51:3), TG(52:0), TG(52:1), TG(52:1), TG(52:2), TG(52:2), TG(52:3), TG(52:4), TG(52:5), TG(54:2), TG(54:2), TG(54:3), TG(54:3), TG(54:4), TG(54:4), TG(54:5), TG(54:6), TG(56:5), TG(56:5), TG(56:6), TG(56:7), TG(56:8), TG(56:9), and TG58:8).