WO2003060518A1 - Diagnostic de schizophrenie - Google Patents

Diagnostic de schizophrenie Download PDF

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Publication number
WO2003060518A1
WO2003060518A1 PCT/JP2003/000292 JP0300292W WO03060518A1 WO 2003060518 A1 WO2003060518 A1 WO 2003060518A1 JP 0300292 W JP0300292 W JP 0300292W WO 03060518 A1 WO03060518 A1 WO 03060518A1
Authority
WO
WIPO (PCT)
Prior art keywords
growth factor
basic
schizophrenia
fibroblast growth
antibody
Prior art date
Application number
PCT/JP2003/000292
Other languages
English (en)
Japanese (ja)
Inventor
Kenji Hashimoto
Masaomi Ito
Eiji Shimizu
Original Assignee
Japan Science And Technology Agency
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Japan Science And Technology Agency filed Critical Japan Science And Technology Agency
Publication of WO2003060518A1 publication Critical patent/WO2003060518A1/fr

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Classifications

    • 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
    • G01N33/6872—Intracellular protein regulatory factors and their receptors, e.g. including ion channels
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/475—Assays involving growth factors
    • G01N2333/50—Fibroblast growth factors [FGF]

Definitions

  • the present invention relates to a diagnostic agent for spirituality, more specifically, antibasic! ⁇ 1
  • a diagnostic agent for schizophrenia containing bud growth factor antibody as a main component Conventional technology
  • Schizophrenia occurs in about 1% of the population and occurs in adolescents and young people in their twenties. Symptoms include positive symptoms such as hallucinations and delusions, negative symptoms such as dull emotion, decreased motivation, social withdrawal, and cognitive impairment. Due to the special nature of the disease, it is desired to establish a comprehensive treatment system including early diagnosis, treatment, rehabilitation activities, and prevention of recurrence. Drug treatment is indispensable for the treatment of mental retardation, and Hue.
  • Inhaled compounds petilophenone compounds, benzamide compounds, iminol compounds, chepin compounds, indole compounds, and serotonin 'dopamine receptor blockers have been administered.
  • the basic bud growth factor focused on in the present invention has a growth promoting effect not only on Okiblasts but also on many cell lines and modifies the differentiation function of cells.
  • it is also known to have neuroprotective effects such as an inhibitory effect on apoptosis.
  • Basic fibroblast growth factor is overexpressed in many malignant tumors, and it is speculated that it is involved in tumor growth.
  • the role of basic germ growth factor in psychiatric and neurological disorders such as psychiatry and psychiatric disorders is not known at all.
  • An object of the present invention is to provide such a diagnostic agent and a diagnostic method.
  • the present inventors have found that the level of basic fibroblast growth factor in the serum of schizophrenic patients is significantly increased as compared with that of healthy subjects, and completed the present invention based on such findings. I let it.
  • the present invention is a diagnostic agent for schizophrenia, which comprises an antibasic bud growth factor antibody as an active ingredient.
  • the anti-basic occlusion growth factor antibody may be labeled.
  • the present invention is also a method for diagnosing schizophrenia, comprising measuring the concentration of chlorophyll fibroblast growth factor in the serum of a patient using these diagnostic agents. Further, the present invention is a method for determining a therapeutic agent for a mental component using these diagnostic agents.
  • the present invention provides a diagnostic kit comprising an anti-basic »bud growth factor antibody or a labeled anti-basic fibroblast growth factor antibody as a main component, and the use of these schizophrenia diagnostic kits in the serum of patients. It is a method for diagnosing schizophrenia comprising measuring the concentration of basic H bud growth factor.
  • the present invention is also a method for assaying a therapeutic agent for schizophrenia using an anti-basic fibroblast growth factor antibody or a labeled anti-basic fibroblast growth factor antibody.
  • the “anti-basic refractory growth factor antibody” in the present invention is an antibody purified using a basic fibroblast growth factor as an antigen, as long as it has an ability to bind to basic »i bud growth factor.
  • a basic fibroblast growth factor as an antigen
  • “Labeled anti-basic fibroblast growth factor antibody” is used to convert basic fibroblast growth factor antibody to peroxidase, ⁇ -D-galactosidase, allyl phosphatase, glucose-6-phosphate dehydratase, etc.
  • “labeled anti-basic Ht bud growth factor antibody” also includes an anti-basic fibroblast growth factor antibody modified with piotin, 2,4-dinitrophenol, or the like. In this case, the quantification can be further performed by further using avidin labeled with the labeled anti-basic growth factor antibody and a labeled anti-2,4-jetrophenol antibody.
  • Diagnosis of schizophrenia by this effort can be performed, for example, as follows. Serum is prepared from human blood, and the amount of basic »bud growth factor in the serum is determined by various methods. Desirably, basic fibroblast growth factor is detected and quantified by a sandwich ELISA using an antibody having high specificity for basic sprouts. Diagnosis of schizophrenia is based on the fact that the concentration of basic bud growth factor in serum of schizophrenic patients is significantly higher than that of healthy subjects.
  • Specific methods for measuring basic fibroblast growth factor in serum include, for example,
  • a step of immobilizing an anti-basic »budding growth factor antibody on a solid phase such as polystyrene, nylon, glass, silicon rubber, or Sepharose;
  • a method comprising the step of measuring the amount of basic sprouts using the label.
  • specific methods for measuring basic occlusion growth factor in serum include, for example,
  • a step of immobilizing an anti-basic ⁇ -budding factor antibody on a solid phase such as polystyrene, nylon, glass, silicon wrapper, or sepharose;
  • a method comprising the step of measuring the amount of basic fibroblast growth factor using the label.
  • a step of immobilizing an anti-basic »fibroblast growth factor antibody on a solid phase such as polystyrene, nylon, glass, silicone rubber, or sepharose;
  • a method comprising the step of measuring the amount of basic germ growth factor using the label; a powerful method.
  • Examples of the shape of the solid phase include a small sphere, a well, and a test tube.
  • Basic fibroblast growth factor used as an antigen or an ELISA standard can be adjusted by using commercially available products or by the following method.
  • a gene encoding basic fibroblast growth factor (GeneBank number: M34641) is inserted into an appropriate vector, inserted into an appropriate host, transformed, and cultured.
  • Recombinant basic fiber from supernatant A fibroblast growth factor can be obtained, and it is suitable for production of a large amount of basic bud growth factor.
  • the host cell is not particularly limited, and various host cells conventionally used in genetic engineering techniques, for example, Escherichia coli, Bacillus subtilis, yeast, plants or animal cells can be used.
  • Anti-basic germinal growth factor antibody is prepared by immunizing egrets, -birds, and turkeys with basic fibroblast growth factor as an antigen.
  • the labeled anti-basic growth factor antibody can be prepared by reacting the anti-basic fiber growth factor antibody with a commercially available kit of biotinylation reagent or peroxidase with a crosslinking agent. it can.
  • the present invention is also useful for determining a therapeutic drug for schizophrenia. That is, a compound having an effect of reducing basic fibroblast growth factor may be useful as a therapeutic drug for schizophrenia.
  • model animals with high levels of basic fibroblast growth factor such as mouse rats are also useful as models for mental components. Therefore, it is possible to screen new schizophrenia drugs by using this test method.
  • Therapeutic agents found in such a manner can include those that can be administered parenterally or orally.
  • the exact dosage and dosage regimen for the therapeutic agent will need to be determined by the requirements of the individual treatment symptom, the method of treatment, the degree of illness or need, and, of course, the judgment of the physician.
  • the dosage and frequency of parenteral administration vary depending on symptoms, age, body weight, dosage form, etc.For example, when administered subcutaneously or intravenously as an injection, adult patient weight: L kg, per day
  • the dosage is selected from the range of about 0.1 mg to about 250 mg, preferably from about 1 mg to about 50 mg, e.g., when administered to the trachea as a spray, the weight of an adult patient is 1 kg,
  • the dosage is selected from the range of about 0.1 mg to about 250 Omg per day, preferably the range of about lmg to about 50 Omg.
  • Dosage regimens include daily or intermittent dosing or a combination thereof.
  • the dose and frequency of oral administration vary depending on symptoms, age, body weight, dosage form, etc.S, for example, adult patient weight 1 kg, range from about 0.5 mg to about 250 mg per day, Preferably, the dose is selected from the range of about lmg to about 100 Omg.
  • a pharmaceutical composition comprising mixing the therapeutic agent for schizophrenia obtained by the method of the present invention with a pharmaceutically acceptable non-toxic carrier.
  • Such compositions are particularly suitable for parenteral administration (for subcutaneous injection, intramuscular injection, or intravenous administration, especially in solution or suspension form), and particularly for vaginal or rectal administration, in particular, for the purpose of preparation.
  • Semi-solid dosage forms such as ⁇ -mums or suppositories are preferred, and for nasal administration, powders, nasal drops, or aerosol formulations are particularly preferred.
  • compositions can be administered in single-dose form and can be administered in a pharmaceutical technology such as that described, for example, in Remington's Pharmaceutical Sciences (Mac Publissing 'Company, Easton, PA, 1970). It can be prepared by any of the well-known methods. Injectable preparations may contain, as pharmaceutical carriers, plasma-derived proteins such as albumin, amino acids such as glycine, and sugars such as mannitol.
  • a buffer When used in an injectable form, a buffer, a solubilizing agent, an isotonic agent and the like can be further added.
  • a surfactant such as Tween80 (registered trademark) or Tween20 (registered trademark) to prevent the preparation.
  • Parenteral dosage forms other than injections may contain distilled water or physiological saline, polyalkylene glycols such as polyethylene glycol, oils of plant origin, hydrogenated naphthalene, and the like.
  • Formulations for vaginal or rectal administration for example suppositories, contain, as common excipients, for example, polyalkylene glycol, petrolatum, cocoa oil and the like.
  • Vaginal preparations may contain absorption enhancers such as bile salts, ethylenediamine salts, citrate salts and the like.
  • Formulations for inhalation may be solid, may contain, for example, ratatose as an excipient, and nasal drops may be a water or oil solution.
  • Example 1 the present invention will be illustrated by way of examples, but these are not intended to limit the present invention.
  • Example 1 the present invention will be illustrated by way of examples, but these are not intended to limit the present invention.
  • the test in this example was performed on 20 schizophrenic patients and 20 healthy subjects.
  • a 96-well plate buffer solution 100 ⁇ L ⁇ coated with an anti-basic »t bud growth factor antibody was added, and 150 ⁇ L of serum was added for tl.
  • a solution to which human basic arrowhead bud growth factor (legZmL) is added After reacting at room temperature for 3 hours, wash with buffer 6 times, add anti-basic fibroblast growth factor antibody labeled with AL-phosphorphos- phatase and react at room temperature for 2 hours. After washing 6 times with buffer, add NADPH (50 ⁇ L) containing a stabilizer and incubate at room temperature for 45 minutes.
  • NADPH 50 ⁇ L
  • Example 2 An untreated patient (9 patients) and a patient under treatment (11 patients) were examined in the same manner as in Example 1.

Abstract

L'invention concerne un diagnostic de schizophrénie, notamment un diagnostic de schizophrénie contenant un anticorps agissant contre un facteur de croissance de fibroblaste de base comme principe actif. On diagnostique la schizophrénie par analyse du facteur de croissance du fibroblaste de base dans le sérum à l'aide de l'anticorps précité.
PCT/JP2003/000292 2002-01-15 2003-01-15 Diagnostic de schizophrenie WO2003060518A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2002006212A JP2003212795A (ja) 2002-01-15 2002-01-15 精神分裂病の診断薬
JP2002-6212 2002-01-15

Publications (1)

Publication Number Publication Date
WO2003060518A1 true WO2003060518A1 (fr) 2003-07-24

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2003/000292 WO2003060518A1 (fr) 2002-01-15 2003-01-15 Diagnostic de schizophrenie

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JP (1) JP2003212795A (fr)
WO (1) WO2003060518A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5288365B2 (ja) 2007-07-17 2013-09-11 学校法人東海大学 統合失調症の検査および治療

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001169793A (ja) * 1990-03-29 2001-06-26 Scios Inc 同一のｎ末端を有する塩基性繊維芽細胞増殖因子の高レベル発現
US6277820B1 (en) * 1998-04-09 2001-08-21 Genentech, Inc. Method of dopaminergic and serotonergic neuron formation from neuroprogenitor cells
JP2001245661A (ja) * 2000-03-07 2001-09-11 Univ Niigata 遺伝子発現を指標とする精神分裂病の客観的診断法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001169793A (ja) * 1990-03-29 2001-06-26 Scios Inc 同一のｎ末端を有する塩基性繊維芽細胞増殖因子の高レベル発現
US6277820B1 (en) * 1998-04-09 2001-08-21 Genentech, Inc. Method of dopaminergic and serotonergic neuron formation from neuroprogenitor cells
JP2001245661A (ja) * 2000-03-07 2001-09-11 Univ Niigata 遺伝子発現を指標とする精神分裂病の客観的診断法

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