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WO2011003623A2 - Procédé et marqueurs pour le pronostic individuel et/ou la détection individuelle d'une neuropathie - Google Patents

Procédé et marqueurs pour le pronostic individuel et/ou la détection individuelle d'une neuropathie Download PDF

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Publication number
WO2011003623A2
WO2011003623A2 PCT/EP2010/004197 EP2010004197W WO2011003623A2 WO 2011003623 A2 WO2011003623 A2 WO 2011003623A2 EP 2010004197 W EP2010004197 W EP 2010004197W WO 2011003623 A2 WO2011003623 A2 WO 2011003623A2
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WIPO (PCT)
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car3
pparg
igfbp5
ssg1
thrsp
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PCT/EP2010/004197
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German (de)
English (en)
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WO2011003623A3 (fr
Inventor
Michael Sereda
Robert Fledrich
Moritz Rossner
Sven Wichert
Klaus Armin Nave
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MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V.
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Priority claimed from DE200910032418 external-priority patent/DE102009032418A1/de
Priority claimed from DE200910042090 external-priority patent/DE102009042090A1/de
Application filed by MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. filed Critical MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V.
Publication of WO2011003623A2 publication Critical patent/WO2011003623A2/fr
Publication of WO2011003623A3 publication Critical patent/WO2011003623A3/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/118—Prognosis of disease development
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/28—Neurological disorders

Definitions

  • the present invention relates to a method for the individual prognosis of the occurrence and / or the course of a neuropathy and / or for the individual diagnosis of a neuropathy of a mammal, in particular a human. It further relates to suitable markers and uses of these markers.
  • CMT Charcot-Marie-Tooth disease
  • the disease leads to chronic progressive, symmetrical, distally marked muscle atrophy, especially in the lower extremities.
  • the disabilities that increase with age range from gait insecurity to towards wheelchair accessibility.
  • the average age at onset of first symptoms is around 20 years.
  • the severity and the age of onset of the disease vary greatly between individual patients and even siblings despite the same underlying genetic defect. So far, no explanation for this biological phenomenon has been found, although it would be of great interest for CMT patients to know their individual disease prognosis.
  • the object of the present invention is to provide a method for individual prognosis or individual diagnosis of neuropathy and suitable markers for this purpose indicate.
  • markers ADIPOQ, LPL, PPARG, THRSP, CAR3, IGFBP5, NEFL, NEFM, CLDN1, SCD1, CDO1, GDNF, RBP4, NEXN, EBF1, IL1R1, PRX, SPRR1A, SSG1, TGFB3, CXCL12, PMP22 and ID3 are included of the present invention are markers which allow an individual prognosis of the occurrence or the course of a neuropathy in a mammal, in particular in a human. These markers have been found to be suitable for this purpose according to the present invention. Of these markers are especially the markers
  • ADIPOQ, LPL, PPARG, THRSP, CAR3, IGFBP5, NEFL, NEFM, CLDN1, TGFB3, CXCL12, PMP22 and ID3 have been found to be particularly suitable.
  • these markers are suitable individually or else in any combination of individual markers, the combination comprising two, three, four, ... (abbreviated "at least two") markers,
  • the marker ADIPOQ with each of the other markers mentioned, the marker LPL with each of the other markers mentioned, etc. are expressly disclosed and suitable for the present invention is thus any combination of these markers in any number of markers for the following groups of markers.
  • the markers ADIPOQ, LPL, PPARG, THRSP, CAR3, IGFBP5, NEFL, NEFM, CLDN1 are particularly suitable for detecting an individual prognosis from nerve cells, in particular from cells of the sciatic nerve.
  • the markers SCD1, CDO1, GDNF, RBP4, NEXN, EBF1, IL1R1, PRX, SPRR1A, SSG1 are also suitable for individual prognosis from nerve cells, in particular cells of the sciatic nerve.
  • the combinations are suitable (in each case a combination of markers is limited by semicolon) IGFBP5, CAR3, PPARG; IGFBP5, CAR3; IGFBP5, PPARG; CAR3 and PPARG; NEFL, NEFM and CLDNl; LPL, PPARG; CLDN1, LPL; IGFBP5, CAR3; IGFBP5, NEFL;
  • IGFBP5 NEFM; IGFBP5, CLDN1; IGFBP5, LPL; IGFBP5, ADIPOQ; IGFBP5, THRSP; IGFBP5; SSGl; CAR3, NEFL;
  • THRSP PPARG, SSG1; IGFBP5, PPARG; IGFBP5, PPARG, and
  • marker combinations are also particularly suitable for prognosis, in particular from nerve cells, in particular from cells of the sciatic nerve:
  • IGFBP5 IGFBP5, PPARG, CAR3, NEFM, NEFL, CLDN1, LPL, ADIPOQ, THRSP, SSG1;
  • IGFBP5 PPARG; IGFBP5, CAR3; IGFBP5, NEFM; IGFBP5, NEFL; IGFBP5, CLDN1; IGFBP5, LPL; IGFBP5, ADIPOQ;
  • IGFBP5 PPARG, SSG1; IGFBP5, CAR3, NEFM; IGFBP5,
  • PPARG PPARG, NEFM, LPL; IGFBP5, PPARG, NEFM, ADIPOQ;
  • IGFBP5 PPARG, NEFM, THRSP; IGFBP5, PPARG, NEFM, SSG1; IGFBP5, PPARG, NEFL, CLDN1; IGFBP5, PPARG, NEFL, LPL; IGFBP5, PPARG, NEFL, ADIPOQ; IGFBP5,
  • PPARG PPARG, NEFL, THRSP; IGFBP5, PPARG, NEFL, SSG1;
  • IGFBP5 PPARG, CAR3, NEFM, NEFL, CLDN1; IGFBP5,
  • IGFBP5 PPARG, CAR3, NEFM, THRSP, SSG1; IGFBP5,
  • IGFBP5 PPARG, CAR3, NEFL, THRSP, SSG1; IGFBP5,
  • IGFBP5 PPARG, NEFM, NEFL, LPL, ADIPOQ; IGFBP5,
  • IGFBP5 PPARG, NEFM, NEFL, THRSP, SSG1; IGFBP5,
  • IGFBP5 PPARG, NEFM, CLDN1, ADIPOQ, SSG1; IGFBP5,
  • IGFBP5 NEFM, NEFL, CLDN1, ADIPOQ, SSG1; IGFBP5,
  • IGFBP5 PPARG, CAR3, NEFM, NEFL, CLDN1, LPL; IGFBP5, PPARG, CAR3, NEFM, NEFL, CLDN1, ADIPOQ; IGFBP5,
  • PPARG PPARG, NEFM, CLDN1, LPL, ADIPOQ, THRSP; IGFBP5,
  • the markers TGFB3, CXCL12, PMP22, ID3 are particularly well suited for prognosis from skin cells; PMP22 to an extraordinary extent.
  • the marker GSTP2 is also suitable for prognosis from skin cells. Again, any combination of these markers is suitable for prediction from skin cells.
  • marker combinations are also particularly suitable for prognosis, in particular from skin cells:
  • Each of the marker combinations, which is particularly suitable for prognosis from nerve cells, in combination with each of the marker combinations, which is called as particularly suitable for prognosis from skin cells, is suitable for prognosis.
  • the individual diagnosis of an existing, possibly also as yet unrecognized, neuropathy of a mammal, in particular a human, according to the present invention can be determined by determining the expression of marker genes from the following group: PPARG, CAR3, NNT, IGF1, IGFBP5, DPT, DDT, IL16,
  • markers PPARG, CAR3, NNT, IGF1, IGFBP5, DPT, DDT, IL16, SPRR1A, SSG1, GSTT2, CTSA, FN3KRP are selected, in particular also marker combinations containing or consisting of GSTT2 and SPRR1A consist.
  • markers mentioned here are particularly suitable for determining the individual diagnosis of neuropathy from skin cells, Again, any combination of these markers with any number of markers, in particular at least two markers, is disclosed and suitable for the present invention
  • the following marker combinations are particularly suitable for diagnosis, in particular from skin cells:
  • IGFBP5 PPARG; IGFBP5, CAR3; IGFBP5, IGFl; IGFBP5, DPT; IGFBP5, DDT; IGFBP5, IL16; IGFBP5, SPRRIA;
  • IGFBP5 SPRRIA, NNT; IGFBP5, SPRRIA, SSGl; IGFBP5, NNT, SSG1; PPARG, CAR3, IGFl; PPARG, CAR3, DPT;
  • PPARG, DDT SSG1; PPARG, IL16, SPRRIA; PPARG, IL16, NNT; PPARG, ILI ⁇ , SSGI; PPARG, SPRRIA, NNT; PPARG, SPRRIA, SSGl; PPARG, NNT, SSG1; CAR3, IGFl, DPT;
  • PPARG, CAR3, DPT, IL16 PPARG, CAR3, DPT, SPRRIA;
  • IGFBP5 PPARG, IGFl, DPT, SSGl; IGFBP5, PPARG, IGF1, DDT, IL16; IGFBP5, PPARG, IGFl, DDT, SPRRIA; IGFBP5, PPARG, IGFl, DDT, NNT; IGFBP5, PPARG, IGF1, DDT, SSG1; IGFBP5, PPARG, IGFl, IL16, SPRRIA; IGFBP5,
  • IGFBP5 PPARG, DDT, ILl ⁇ , NNT; IGFBP5, PPARG, DDT, ILl ⁇ , SSGl; IGFBP5, PPARG, DDT, SPRRIA, NNT; IGFBP5, PPARG, DDT, SPRRIA, SSGl; IGFBP5, PPARG, DDT, NNT, SSG1; IGFBP5, PPARG, ILl ⁇ , SPRRIA, NNT; IGFBP5,
  • IGFBP5 CAR3, IGFl, DPT, SPRRIA; IGFBP5, CAR3, IGFl, DPT, NNT; IGFBP5, CAR3, IGFl, DPT, SSG1; IGFBP5, CAR3, IGFl, DDT, ILl ⁇ ; IGFBP5, CAR3, IGF1, DDT,
  • IGFBP5 IGF1, DDT, IL16, SSG1; IGFBP5, IGF1, DDT,
  • IL16 NNT
  • IGFBP5 DPT, DDT, NNT, SSG1; IGFBP5, DPT, IL16,
  • PPARG IGF1, DDT, NNT, SSG1; PPARG, IGFl, ILl ⁇ ,
  • IGFBP5 PPARG, CAR3, IGFl, DPT, DDT; IGFBP5, PPARG, CAR3, IGFl, DPT, ILI 6; IGFBP5, PPARG, CAR3, IGFl, DPT, SPRRIA; IGFBP5, PPARG, CAR3, IGFl, DPT, NNT;
  • IGFBP5 PPARG, CAR3, IGF1, DPT, SSG1; IGFBP5, PPARG, CAR3, IGF1, DDT, IL16; IGFBP5, PPARG, CAR3, IGFl, DDT, SPRRIA; IGFBP5, PPARG, CAR3, IGFl, DDT, NNT;
  • IGFBP5 PPARG, CAR3, IGF1, DDT, SSG1; IGFBP5, PPARG, CAR3, IGFl, IL16, SPRRIA; IGFBP5, PPARG, CAR3, IGF1, IL16, NNT; IGFBP5, PPARG, CAR3, IGF1, IL16, SSG1;
  • IGFBP5 PPARG, CAR3, IGFl, SPRRIA, NNT; IGFBP5,
  • IGFBP5 PPARG, DPT, DDT, SPRRIA, SSGl
  • IGFBP5 PPARG, DPT, DDT, NNT, SSG1
  • IGFBP5, PPARG, DPT, IL16 PPARG, IL16
  • IGFBP5 CAR3, IGFl, DPT, SPRRIA, SSG1; IGFBP5, CAR3, IGF1, DPT, NNT, SSG1; IGFBP5, CAR3, IGFl, DDT, IL16, SPRRIA; IGFBP5, CAR3, IGF1, DDT, IL16, NNT; IGFBP5,
  • IGFBP5 IGF1, DPT, IL16, SPRRIA, NNT; IGFBP5, IGF1, DPT, IL16, SPRRIA, SSG1; IGFBP5, IGF1, DPT, IL16, NNT, SSG1; IGFBP5, IGFl, DPT, SPRRIA, NNT, SSGl;
  • IGFBP5 IGF1, IL16, SPRRIA, NNT, SSG1; IGFBP5, DPT, DDT, IL16, SPRRIA, NNT; IGFBP5, DPT, DDT, IL16,
  • IGFBP5 PPARG, IGFl, DPT, SPRRIA, NNT, SSGl; IGFBP5, PPARG, IGF1, DDT, IL16, SPRRIA, NNT; IGFBP5, PPARG, IGF1, DDT, IL16, SPRRIA, SSG1; IGFBP5, PPARG, IGF1, DDT, IL16, NNT, SSG1; IGFBP5, PPARG, IGFl, DDT,
  • IGFBP5 PPARG, CAR3, IGF1, DPT, DDT, IL16, SPRRIA; IGFBP5, PPARG, CAR3, IGF1, DPT, DDT, IL16, NNT;
  • IGFBP5 IGFBP5, PPARG, CAR3, IGF1, DPT, DDT, IL16, SSG1;
  • IGFBP5 PPARG, CAR3, IGF1, DPT, DDT, SPRRIA, SSG1; IGFBP5, PPARG, CAR3, IGF1, DPT, DDT, NNT, SSG1;
  • IGFBP5 PPARG, CAR3, IGF1, DPT, IL16, SPRRIA, NNT; IGFBP5, PPARG, CAR3, IGF1, DPT, IL16, SPRRIA, SSG1; IGFBP5, PPARG, CAR3, IGF1, DPT, IL16, NNT, SSG1;
  • IGFBP5 PPARG, CAR3, IGF1, DPT, SPRRIA, NNT, SSG1; IGFBP5, PPARG, CAR3, IGF1, DDT, IL16, SPRRIA, NNT; IGFBP5, PPARG, CAR3, IGF1, DDT, IL16, SPRRIA, SSG1; IGFBP5, PPARG, CAR3, IGF1, DDT, IL16, NNT, SSG1;
  • IGFBP5 PPARG, CAR3, IGF1, DDT, SPRRIA, NNT, SSG1; IGFBP5, PPARG, CAR3, IGF1, IL16, SPRRIA, NNT, SSG1; IGFBP5, PPARG, CAR3, DPT, DDT, IL16, SPRRIA, NNT;
  • IGFBP5 PPARG, CAR3, DPT, DDT, IL16, SPRRIA, SSG1;
  • IGFBP5 PPARG, IGF1, DPT, DDT, IL16, SPRRIA, SSG1;
  • IGFBP5 PPARG, IGF1, DPT, IL16, SPRRIA, NNT, SSG1; IGFBP5, PPARG, IGF1, DDT, IL16, SPRRIA, NNT, SSG1; IGFBP5, PPARG, DPT, DDT, IL16, SPRRIA, NNT, SSGl;
  • IGFBP5 CAR3, IGF1, DPT, DDT, IL16, SPRRIA, NNT; IGFBP5, CAR3, IGF1, DPT, DDT, IL16, SPRRIA, SSG1;
  • IGFBP5 IGFBP5, CAR3, IGF1, DPT, DDT, IL16, NNT, SSG1;
  • IGFBP5 IGFBP5, CAR3, IGF1, DDT, IL16, SPRRIA, NNT, SSG1;
  • IGFBP5 IGF1, DPT, DDT, IL16, SPRRIA, NNT, SSG1;
  • PPARG PPARG, CAR3, IGF1, DPT, DDT, IL16, SPRRIA, NNT;
  • PPARG PPARG, CAR3, IGF1, DPT, DDT, IL16, SPRRIA, SSG1;
  • IGFBP5 IGFBP5, PPARG, CAR3, IGF1, DPT, DDT, ILl ⁇ , SPRRIA, NNT, SSGl.
  • the combination of IGFBP5, CAR3, PPARG and SSGl is suitable for diagnostic conclusions about CMT from skin cells.
  • Figure 1 is the protocol used in this experimental approach
  • Figure 2 shows the structure of the sciatic nerve
  • FIG. 3 shows the handle strength test
  • Figure 4 further details from the experimental approach
  • FIG. 5 shows the results of a validation of differentially regulated genes between phenotypically strong and weakly affected CMT rats.
  • FIG. 6 shows the results of a validation of the genes
  • CMT rats were harvested from the skin or from the distal portion of the sciatic nerve already prior to the onset of the disease, at the age of seven days, of peripheral nerve biopsy ( Figures 1, 2, 4). The removal took place under deep anesthesia by intraperitoneal injection of ketamine and xylazine.
  • the CMTLA disease course of the biopsied animals was regularly quantified over two months using the front leg grip strength test (FIG. 3). After this period, the experimental animals were killed by CO 2 anesthesia and their peripheral nervous system was histologically examined (FIG. 1). In this way individuals with severe disabilities and strong peripheral demyelination could be identified.
  • FIG. 5 shows the quotients of the mean expression values (EQ) between strongly affected and weakly affected CMT rats for the genes and tissues examined accordingly.
  • a value EQ> 1 is considered to be highly regulated expression, a value of EQ ⁇ 1 as downregulated expression in severely affected animals.
  • each of the expression levels in Figure 1 is provided with a statistical significance P (T-test).
  • P ⁇ 0.1 was considered relevant, a value of P ⁇ 0.05 was considered statistically significant. Consequently, the genes provided with a P-value ⁇ 0.1 are suitable for the individual prognosis or the individual diagnosis according to the present invention, while the regulated genes provided with a P-value ⁇ 0.05 are suitable individually because of their statistical significance or in combination especially for individual prognosis and individual diagnosis according to the present invention.
  • the expression values recorded by RT-PCR were normalized to the housekeeping genes ACTB and 18SRRNA for dermal tissue and ACTB and CYCPHA for sciatic nerve tissue (sciatic nerve).
  • CMT rats strongly and weakly CMT-affected rats, so-called CMT rats, were identified after manifestation of the phenotype and their skin cells and sciatic nerves in early disease stages (postnatal day 7 (P7), prognostic markers) and their skin biopsies In early stages of the disease (postnatal, day 7 (P7), prognostic markers) and late stage disease (postnatal 9th week (9W), "disease markers”), the results of Figure 5 are confirmed for differentially regulated genes The results can also be transferred to other neuropathies (eg diabetic-related)
  • the present invention thus provides markers and methods which are quite generally applicable to neuropathies (Duration: 1 year) the applicability of the marker demonstrated in the animal model in huma occupied system.
  • CMTNS Charge-Marie-Tooth Neuropathy Score
  • Quantitative RT-PCR was used in all skin biopsies, i.a. the expression of the marker genes GSTT2, FN3KRP and CTSA, which were previously identified in the CMT rat.
  • the marker GSTT2 is a disease marker for the CMTlA, which is present in all 6 CMTNS
  • ADIPOQ adiponectin (adiponectin); LPL: lipoprotein lipase (lipoprotein lipase); SCDI: stearoyl-coenzyme A desaturase 1 (stearoyl-coenzyme A desaturase 1); PPARG: peroxisome proliferator activated receptor gamma (peroxisome proliferator-activated receptor gamma); THRSP: thyroid hormone responsive protein (thyroid hormone-responsive protein); PRKAR2B: protein kinase, cAMP dependent regulatory, type II beta (cAMP-dependent, regulatory protein kinase, type 2 beta); CDOl: cysteine dioxygenase 1
  • Cysteine dioxygenase 1 GSTP2: glutathione S-transferase, pi 2 (glutathione-S-transferase, pi 2); CAR3: carbonic anhydrase 3 (carbonic anhydrase 3); NNT: nicotinamide nucleotide transhydrogenase
  • GDNF glial cell derived neurotrophic factor (neurotrophic factor of glial origin); IGFl: insuline-like growth factor 1 (insulin-like growth factor 1);
  • IGFBP5 insuline-like growth factor binding protein 5 (insulin-like growth factor binding protein 5); RBP4: retinol binding protein 4 (retinol binding protein 4); TGFB3: transforming growth factor, beta 3 (transforming growth factor beta 3); DPT:
  • dermatopontin dermatopontin
  • MYL2_V2 myosine light chain v2 (light chain of myosin, variant 2);
  • NEFL neurofilament light chain (light chain of neurofilament);
  • NEFM neurofilament medium (middle chain of neurofilament);
  • NEXN nexilin (nexilin);
  • CXCL12 chemokine ligand 12, C-X-C motif
  • Phosphodiesterase 2A PDE3B: phosphodiesterase 3B (phosphodiesterase 3B); ID3: inhibitor of DNA binding 3 (inhibitor of DNA binding 3); SPRRIA: small proline-rich repeat protein IA; RIBIN: rRNA promoter binding protein (rRNA promoter binding protein); SSGl: steroid sensitive gene 1 (steroid sensitive gene 1); ACTB: beta actin (actin beta); CYCPHA: cyclophilin A (cyclophilin A); 18SrRNA: 18S ribosomal RNA (18S ribosomal RNA); CTSA: cathepsins A (cathepsin A); GSTT2: glutathione-S-transferase theta 2; FN3KRP: Fructosamine 3-kinase related protein.

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Abstract

L'invention concerne un procédé de pronostic individuel de l'apparition et/ou du déroulement d'une neuropathie et/ou de diagnostic individuel d'une neuropathie chez un mammifère, notamment chez l'homme. L'invention porte également sur des marqueurs appropriés et sur des utilisations de ces marqueurs.
PCT/EP2010/004197 2009-07-09 2010-07-09 Procédé et marqueurs pour le pronostic individuel et/ou la détection individuelle d'une neuropathie WO2011003623A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE102009032418.6 2009-07-09
DE200910032418 DE102009032418A1 (de) 2009-07-09 2009-07-09 Verfahren und Marker zur individuellen Prognose und/oder zur individuellenErfassung einer Neuropathie
DE200910042090 DE102009042090A1 (de) 2009-09-18 2009-09-18 Verfahren und Marker zur individuellen Prognose und/oder zur individuellen Erfassung einer Neuropathie
DE102009042090.8 2009-09-18

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EP2540825A2 (fr) 2011-06-30 2013-01-02 The Procter & Gamble Company Compositions de nettoyage comprenant une référence de variantes dýamylase à une liste de séquences
EP2551336A1 (fr) 2011-07-25 2013-01-30 The Procter & Gamble Company Composition détergente liquide enzymatique stabilisée
CN105886628A (zh) * 2016-04-29 2016-08-24 肖刻 Sprr1a基因在制备骨关节炎诊断产品中的应用
EP3357994A1 (fr) 2017-02-01 2018-08-08 The Procter & Gamble Company Compositions de nettoyage comprenant des variantes d'amylase
CN110261619A (zh) * 2019-06-14 2019-09-20 上海四核生物科技有限公司 Prkar2b蛋白作为胃癌血清生物标志物的应用及其试剂盒
WO2020264552A1 (fr) 2019-06-24 2020-12-30 The Procter & Gamble Company Compositions de nettoyage comprenant des variants d'amylase

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EP2540825A2 (fr) 2011-06-30 2013-01-02 The Procter & Gamble Company Compositions de nettoyage comprenant une référence de variantes dýamylase à une liste de séquences
WO2013003659A1 (fr) 2011-06-30 2013-01-03 The Procter & Gamble Company Compositions de nettoyage contenant des variants d'amylase se référant à une liste de séquences
EP3121270A2 (fr) 2011-06-30 2017-01-25 The Procter & Gamble Company Compositions de nettoyage comprenant une reference de variantes d'amylase a une liste de sequences
EP2551336A1 (fr) 2011-07-25 2013-01-30 The Procter & Gamble Company Composition détergente liquide enzymatique stabilisée
WO2013016368A1 (fr) 2011-07-25 2013-01-31 The Procter & Gamble Company Compositions de détergents
CN105886628A (zh) * 2016-04-29 2016-08-24 肖刻 Sprr1a基因在制备骨关节炎诊断产品中的应用
CN105886628B (zh) * 2016-04-29 2019-03-26 肖刻 Sprr1a基因在制备骨关节炎诊断产品中的应用
EP3357994A1 (fr) 2017-02-01 2018-08-08 The Procter & Gamble Company Compositions de nettoyage comprenant des variantes d'amylase
WO2018144399A1 (fr) 2017-02-01 2018-08-09 The Procter & Gamble Company Compositions de nettoyage comprenant des variants d'amylase
CN110261619A (zh) * 2019-06-14 2019-09-20 上海四核生物科技有限公司 Prkar2b蛋白作为胃癌血清生物标志物的应用及其试剂盒
CN110261619B (zh) * 2019-06-14 2021-06-25 上海四核生物科技有限公司 Prkar2b蛋白作为胃癌血清生物标志物的应用及其试剂盒
WO2020264552A1 (fr) 2019-06-24 2020-12-30 The Procter & Gamble Company Compositions de nettoyage comprenant des variants d'amylase

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