NON-INVASIVE TECHNIQUE FOR CONDUCTING SKIN INFLAMMATORY DISEASE PHARMACO-GENOMIC STUDIES AND DIAGNOSES THEREOF

• US 20100233718A1
• Filed: 04/22/2010
• Published: 09/16/2010
• Est. Priority Date: 10/26/2007
• Status: Abandoned Application

• Current Assignee: Galderma Research And Development Snc (Nestle SA)
• Original Assignee: Galderma Research And Development Snc (Nestle SA)
• Inventors: AUBERT, Jérôme, Voegel, Johannes
• Application Number:
  US12/765,284
• Publication Number:
  US 20100233718A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

Non-invasive techniques to conduct skin inflammatory disease pharmaco-genomic studies and diagnoses thereof feature discriminating biomarkers and genes and in vitro diagnostic methods employing such biomarkers.

Claims

1. A technique for conducting non-invasive skin inflammatory disease/disorders pharmaco-genomic studies, comprising the steps of:

collecting hair follicles non-invasively, and

analyzing gene expression profiling thereof.

2. The technique as defined by claim 1, wherein the disease studied is psoriasis.

3. The technique as defined by claim 1, wherein the hair is collected from the scalp.

4. A method to monitor efficacy of a pharmacological agent in preventing or treating inflammatory skin disease/disorders, comprising the steps of:

administering to a patient in need of such treatment a therapeutically effective amount of a pharmacological agent,

collect non-invasively hair follicles from such patient,

study/determine the gene expression thereof by analysis,

analyze skin affected patient(s'"'"') samples to controls'"'"' samples or to previous skin affected patient(s'"'"') samples without pharmacological agent.

5. Evaluation efficacy method of a pharmacological agent as defined by claim 4, wherein the pharmacological agent is selected from a small molecule drug or a biological agent.

6. The technique as defined by claim 4, wherein the disease is psoriasis.

7. The technique as defined by claim 4, wherein the hair is collected from the scalp.

9. The diagnosis as defined by claim 7, wherein the disease is psoriasis.

10. The diagnosis as defined by claim 7, wherein the hair is collected from the scalp.

11. The diagnosis as defined by claim 7, wherein the analyzing method is Real time PCR.

12. The diagnosis as defined by claim 7, wherein discriminating genes are selected in the following:

Keratin 16 (KRT16);

gap junction protein, beta 2, (connexin

     26) (GJB2);

chitinase 3-like 2 (CHI3L2);

interleukin 8 (IL8);

fatty acid binding protein 5 (FABP5);

interleukin 1, beta (IL1B);

signal transducer and activator of transcription (STAT1);

heparanase (HPSE);

solute carrier family 6 (amino acid transporter), member 14 (SLC6A14);

transcobalamin I (vitamin B12 binding protein, R binder family) (TCN1);

tumor necrosis factor (TNF);

interleukin 1 family, member 5 (delta) (ID1F5);

small proline-rich protein 2D (SPRR2D);

kallikrein 13 (KLK13);

chemokine (C-X-C motif) ligand 10 (CXCL10);

desmoglein 3 (pemphigus vulgaris antigen) (DSG3);

S100 calcium binding protein Al 2 (S100A12);

interleukin 1 receptor antagonist (IL1RN);

superoxide dismutase 2, mitochondrial (SOD2);

keratin 6C;

(KRT6E);

interferon-induced protein with tetratricopeptide repeats 3 (IFIT3);

desmocollin 2 (DSC2);

endothelial cell growth factor 1 (platelet-derived) (ECGF1);

RAS guanyl releasing protein 2 (calcium and DAG-regulated) (RASGRP2);

wingless-type MMTV integration site family, member 5A (WNT5A);

myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (mouse) (MX1);

small proline-rich protein 1A (SPRR1A);

defensin, beta 4 (DEFB4);

S100 calcium binding protein A9 (S100A9);

interleukin 1 family, member 9 (IL1F9);

kallikrein 6 (neurosin, zyme) (KLK6);

matrix metallopeptidase 9 (MMP9);

serpin peptidase inhibitor, clade B (ovalbumin), member 3 (SERPINB3);

interferon, gamma (IFNG);

lipocalin 2 (oncogene 24p3) (LCN2);

interferon, alpha-inducible protein 27 (IFI27);

peroxisome proliferator-activated receptor delta (PPARD);

serpin peptidase inhibitor, clade B (ovalbumin), member 1 (SERPINB1);

latent transforming growth factor beta binding protein 1 (LTBP1);

pre-B-cell colony enhancing factor 1 (PBEF1);

transglutaminase 1 (K polypeptide epidermal type I, protein-glutamine-gamma-glutamyltransferase) (TGM1);

chemokine (C-C motif) ligand 20 (CCL20);

aldo-keto reductase family 1, member B10 (aldose reductase) (AKR1B10);

S100 calcium binding protein A7 (S100A7).

8. A non-invasive diagnosis of inflammatory skin disease/disorders, comprising the steps of:

collect non-invasively hair follicles,

study/determine the gene expression thereof by analysis,

clusterize control samples to skin affected patient(s'"'"') samples (specific embodiment psoriatic samples) based discriminating genes.

13. The diagnosis as defined by claim 8, wherein discriminating genes are selected in the following:

interleukin 8 (IL8);

beta 4defensin (DEFB4);

S100 calcium binding protein A7 (S100A7);

S100 calcium binding protein A9 (calgranulin B) (S100A9);

S100 calcium binding protein A12 (S100A12);

interleukin 1b (IL-1b);

lipocalin 2 (oncogene 24p3) (LCN2);

transcobalamin I (vitamin B12 binding protein, R binder family) (TCN1);

Interferon alpha-inducible protein 27 (IFI27);

Peroxisome proliferator-activated receptor-PPAR-δ

);

serpin peptidase inhibitor, clade B (ovalbumin), member 3(SERPIN B3).

14. A method to monitor skin or scalp inflammation in a skin affected patient, comprising the steps of:

collect non-invasively patient'"'"'s hair follicles,

study/determine the gene expression by analysis,

analyze inflammation gene (s) from said inflammatory skin affected patient(s'"'"') samples to controls'"'"' samples.

15. A method to monitor skin or scalp inflammation in a psoriatic patient, comprising the steps of:

collect non-invasively patient'"'"'s hair follicles,

study/determine the gene expression by analysis,

analyze inflammation gene (s) from said inflammatory skin affected patient(s'"'"') samples to controls'"'"' samples or to previous patient psoriatic samples.

16. A predictive model of inflammatory skin affected patient(s'"'"') determination, comprising monitoring the modulation in expression of at least 1 discriminating genes or markers selected from the inflammatory markers.

17. The predictive model as defined by claim 16, wherein inflammatory skin affected patient(s'"'"') is psoriatic patient.

18. Discriminating genes or markers included in the model as defined by claim 17, selected from the following:

interleukin 8 (IL8);

beta 4defensin (DEFB4);

S100 calcium binding protein A7 (S100A7);

S100 calcium binding protein A9 (calgranulin B) (S100A9);

S100 calcium binding protein A12 (S100A12);

interleukin 1b (IL-1b);

lipocalin 2 (oncogene 24p3) (LCN2);

transcobalamin I (vitamin B12 binding protein, R binder family) (TCN1);

Interferon alpha-inducible protein 27 (IFI27);

Peroxisome proliferator-activated receptor-PPAR-δ

);

serpin peptidase inhibitor, clade B (ovalbumin), member 3 (SERPIN B3).

19. Psoriatic scalp lesions biomarkers and/or gene expression products as biomarkers selected from among the following:

interleukin 8 (IL8);

beta 4defensin (DEFB4);

S100 calcium binding protein A7 (S100A7);

S100 calcium binding protein A9 (calgranulin B) (S100A9);

S100 calcium binding protein A12 (S100A12);

interleukin 1b (IL-1b);

lipocalin 2 (oncogene 24p3) (LCN2);

transcobalamin I (vitamin B12 binding protein, R binder family) (TCN1);

Interferon alpha-inducible protein 27 (IFI27);

Peroxisome proliferator-activated receptor-PPAR-δ

);

serpin peptidase inhibitor, clade B (ovalbumin), member 3 (SERPIN B3).