Uses of aldose-1-epimerase (mutarotase) for diagnosis and therapy of inflammatory diseases and sepsis

• US 20050130242A1
• Filed: 11/29/2002
• Published: 06/16/2005
• Est. Priority Date: 12/07/2001
• Status: Active Grant

• Current Assignee: B·R·A·H·M·S GmbH (Thermo Fisher Scientific Incorporated)
• Original Assignee: B.R.A.H.M.S Aktiengesellschaft
• Inventors: Struck, Joachim, Bergmann, Andreas, Uhlein, Monika
• Granted Patent: US 7,157,081 B2
• Time in Patent Office: Days
• US Class Current: 435/7.920
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: G01N 2333/99 Isomerases (5.)
• CPC Class Codes: G01N 2800/26 Infectious diseases, e.g. generalised sepsis
• CPC Class Codes: G01N 33/56911 Bacteria
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

Uses of aldose 1-epimerase (SEQ ID NO:3) from body fluids or body tissues in human and veterinary medicine as a marker peptide for diagnosis, for prognosis of the course and for monitoring of the course of inflammations and infections and/or as a target for therapeutically influencing the course of inflammations and/or infections.

Claims

1. Use of aldose 1-epimerase (A1E) from body fluids or body tissues in human and veterinary medicine as a marker peptide for diagnosis, for prognosis of the course and for monitoring of the course of inflammations and infections and/or as a target for therapeutically influencing the course of inflammations and/or infections.

2. Use of aldose 1-epimerase according to claim 1 in differential early diagnosis and detection, for prognosis of the course, for assessment of the severity and for therapy-accompanying assessment of the course of sepsis and severe infections, in particular sepsis-like systemic infections, by determination of the occurrence and/or of the amount of aldose 1 -epimerase in a biological fluid or a tissue sample of a patient.

10. Use of aldose 1 -epimerase according to claim 1 as a means for prophylactic or therapeutic influencing of the course of inflammatory diseases and infections, including sepsis.

3. Method for differential early diagnosis and detection, for prognosis of the course and assessment of the severity and for therapy-accompanying assessment of the course of sepsis and severe infections, in particular sepsis-like systemic infections, characterized in that the presence and/or amount of human aldose 1 -epimerase (SEQ ID NO:

3) in a biological fluid or a tissue sample of a patient is determined and conclusions are drawn from the detectability and/or amount thereof with regard to the presence, the expected course, the severity or the success of a therapy of the sepsis or of infection.

4. Method according to claim 3, characterized in that it is an immunodiagnostic assay method.

5. Method according to claim 3, characterized in that the determination of aldose 1-epimerase is carried out indirectly as a determination of the associated A1E-mRNA or of the A1E enzyme activity.

6. Method according to claim 3, characterized in that it is carried out as part of a multiparameter determination in which at least one further sepsis parameter is simultaneously determined and a measured result in the form of a set of at least two measured quantities, which is evaluated for fine sepsis diagnosis, is obtained.

7. Method according to claim 6, characterized in that, in the course of the multiparameter determination, at least one further parameter which is selected from the group consisting of procalcitonin, CA 19-9, CA 125, S100B, S100A proteins, soluble cytokeratin fragments, in particular CYFRA 21, TPS and/or soluble cytokeratin 1 fragments (sCY1F), the peptides inflammin and CHP, peptide prohormones, glycine N-acyltransferase (GNAT) and the C-reactive protein (CRP) is determined in addition to aldose 1 -epimerase.

8. Method according to claim 6, characterized in that the multiparameter determination is carried out as a simultaneous determination by means of a chip technology measuring apparatus or an immunochromatographic measuring apparatus.

9. Method according to claim 8, characterized in that the evaluation of the complex measured result obtained by means of the measuring apparatus is carried out with the aid of a computer program.

15. Method according to claim 7, characterized in that the multiparameter determination is carried out as a simultaneous determination by means of a chip technology measuring apparatus or an immunochromatographic measuring apparatus.

11. Pharmaceutical composition for the treatment of inflammations, including systemic inflammations, characterized in that it comprises aldose 1-epimerase or a functional partial peptide thereof and a pharmaceutically acceptable carrier.

12. Pharmaceutical composition for the treatment of inflammatory and other stress reactions of the body, characterized in that it contains antibodies produced against aldose 1-epimerase or aldose 1-epimerase fragments or processed aldose 1 -epimerase and prepared for administration to patients, together with a suitable pharmaceutical carrier.

13. Pharmaceutical composition for the treatment of inflammatory diseases of the body, in particular systemic inflammations, or of inflammations caused by infection, in which there is the danger of a systemic spread, characterized in that it contains an active substance which completely or partly inhibits the enzyme activity of aldose 1-epimerase and a suitable pharmaceutical carrier.

14. lmmunoadsorbent which has a solid phase for the selective binding of aldose 1-epimerase from the blood circulation of a patient, for the treatment of inflammations and sepsis.