JP2020533306A - 糖尿病の処置および予防における遺伝子型層別化 - Google Patents
糖尿病の処置および予防における遺伝子型層別化 Download PDFInfo
- Publication number
- JP2020533306A JP2020533306A JP2020513715A JP2020513715A JP2020533306A JP 2020533306 A JP2020533306 A JP 2020533306A JP 2020513715 A JP2020513715 A JP 2020513715A JP 2020513715 A JP2020513715 A JP 2020513715A JP 2020533306 A JP2020533306 A JP 2020533306A
- Authority
- JP
- Japan
- Prior art keywords
- haplotype
- individual
- treatment
- hla
- insulin
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 27
- 230000002265 prevention Effects 0.000 title claims abstract description 7
- 206010012601 diabetes mellitus Diseases 0.000 title description 15
- 238000013517 stratification Methods 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 26
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 6
- 238000011269 treatment regimen Methods 0.000 claims abstract description 5
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 52
- 239000000427 antigen Substances 0.000 claims description 35
- 102000054766 genetic haplotypes Human genes 0.000 claims description 31
- 102000004877 Insulin Human genes 0.000 claims description 27
- 108090001061 Insulin Proteins 0.000 claims description 27
- 229940125396 insulin Drugs 0.000 claims description 26
- 108091022930 Glutamate decarboxylase Proteins 0.000 claims description 24
- 102100035902 Glutamate decarboxylase 1 Human genes 0.000 claims description 23
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 21
- 108091007433 antigens Proteins 0.000 claims description 20
- 102000036639 antigens Human genes 0.000 claims description 20
- 229940037003 alum Drugs 0.000 claims description 6
- 230000001747 exhibiting effect Effects 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 108010086066 HLA-DR8 antigen Proteins 0.000 claims description 5
- 238000007920 subcutaneous administration Methods 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 238000009472 formulation Methods 0.000 claims description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 2
- 238000007918 intramuscular administration Methods 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 239000000902 placebo Substances 0.000 description 10
- 229940068196 placebo Drugs 0.000 description 10
- 108010064885 HLA-DR3 Antigen Proteins 0.000 description 8
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 7
- VOUAQYXWVJDEQY-QENPJCQMSA-N 33017-11-7 Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)CCC1 VOUAQYXWVJDEQY-QENPJCQMSA-N 0.000 description 6
- 108010075254 C-Peptide Proteins 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 108010046732 HLA-DR4 Antigen Proteins 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 210000001165 lymph node Anatomy 0.000 description 4
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 3
- 229930003316 Vitamin D Natural products 0.000 description 3
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 208000018914 glucose metabolism disease Diseases 0.000 description 3
- 210000004153 islets of langerhan Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000008774 maternal effect Effects 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 230000035935 pregnancy Effects 0.000 description 3
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 3
- 235000019166 vitamin D Nutrition 0.000 description 3
- 239000011710 vitamin D Substances 0.000 description 3
- 150000003710 vitamin D derivatives Chemical class 0.000 description 3
- 229940046008 vitamin d Drugs 0.000 description 3
- 102000008214 Glutamate decarboxylase Human genes 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 210000004324 lymphatic system Anatomy 0.000 description 2
- 238000007410 oral glucose tolerance test Methods 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000000391 smoking effect Effects 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 101150014889 Gad1 gene Proteins 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 206010048461 Genital infection Diseases 0.000 description 1
- 208000002705 Glucose Intolerance Diseases 0.000 description 1
- 108010048896 HLA-D Antigens Proteins 0.000 description 1
- 108010065026 HLA-DQB1 antigen Proteins 0.000 description 1
- 206010024971 Lower respiratory tract infections Diseases 0.000 description 1
- 108700005092 MHC Class II Genes Proteins 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108010076181 Proinsulin Proteins 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 210000002660 insulin-secreting cell Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000018773 low birth weight Diseases 0.000 description 1
- 231100000533 low birth weight Toxicity 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 201000009104 prediabetes syndrome Diseases 0.000 description 1
- 108010066381 preproinsulin Proteins 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000004906 toe nail Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0008—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
-
- 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
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56966—Animal cells
- G01N33/56977—HLA or MHC typing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
-
- 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
- C12Q2600/156—Polymorphic or mutational markers
-
- 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
- C12Q2600/172—Haplotypes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/04—Endocrine or metabolic disorders
- G01N2800/042—Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Abstract
Description
様々な遺伝子型を有する患者は、ベータ細胞の分解を引き起こす抗体の様々な組および発達を有する。これは次に、どの抗体が患者において誘発されるかに基づいて、疾患進行における差をもたらす。
一実施形態において、HLA DR3−DQ2ハプロタイプを有し、任意選択でGADAを最初に示す個体は、少なくともGAD自己抗原による処置に供される。
一実施形態において、インスリン自己抗原の投与は、経口、舌下、筋内、皮内またはリンパ内である。
一態様において、本発明は、上記に記載の方法における自己抗原としての使用のためのGADに関する。
本明細書で使用される全ての用語は、本開示の文脈において当業者によりそれらに与えられる意味を有すると意図される。いくつかの用語は、曖昧さを避けるために以下に特に定義する。
以下の実施例は、本発明をさらに例示することを目的とする。実施例は、附属の特許請求の範囲により定義される本発明の範囲を限定するとは考えられるべきではない。
Wherrett DKら(Lancet、2011年7月23日;378巻(9788号):319〜27ページ)は、100日以内にT1Dと診断された3〜45歳の対象における3アーム(A:3sc×20μg GAD−アラム(n=48);B:2×20μg GAD−アラムおよび1つのアラム(n=49);およびC:3×アラム(n=48))ランダム化研究から、1年で、年齢、性別およびベースラインCペプチド値について調節したCペプチドの2時間AUCは、A GAD−アラム群で0.412nmol/L(0.349〜0.478)、B GAD−アラム+アラム群で0.382nmol/L(0.322〜0.446)、およびC アラム群で0.413nmol/L(0.351〜0.477)であり、それぞれ、GAD−アラム×3、GAD−アラム×2およびアラム×3についてベースライン平均値の44%、42%および41%の、1年でのCペプチド平均値の低下に対応することを報告した。著者らは、ベースラインおよび1年でのCペプチドのレベルは、診断の3カ月以内に処置された対象における3つの他のTrialNet研究の対照群での発見を反映したこと、また、これは、アラム単独が12カ月でインスリン分泌の低下に対して効果を有しないことを示すことを指摘している。
多数の膵島自己抗体を有するが、まだインスリン要求糖尿病を有しない50人の健康な小児におけるランダム化二重盲検プラセボ対照研究(DiaPREV−IT、ClinicalTrials.gov識別子:NCT01122446)から、GAD−アラムでの予防処置は、臨床T1Dの開始への進行に影響を及ぼさないことが分かった。
Taviraら(Journal of Diabetes Research、2018年号、記事番号9391845)により説明されるように、12人の開始初期T1D患者において、オープン研究が行われ、アラム中に製剤化された4μgのGADを、鼠径部リンパ節に3回、各回の注射間に30日の期間を伴って、直接注射した。本発明の主題と一致して、DR3−DQ2ハプロタイプを有する患者の処置は、DR3−DQ2ハプロタイプを有しない患者よりも良好なHbA1cデータおよび刺激されたCペプチド曲線下面積データをもたらすことが分かった。
Claims (15)
- 個体における自己免疫疾患の処置または予防のための方法であって、
− 前記個体のHLAハプロタイプを決定することと;
− 前記個体を前記ハプロタイプに基づく処置レジメンに供することと
を含む方法。 - − 前記個体の前記HLAハプロタイプを決定することと;
− 前記個体において前記自己免疫疾患に関連する初期発生自己抗体の特異性を決定することと;
− 前記個体を前記ハプロタイプおよび前記初期発生自己抗体の特異性に基づく処置レジメンに供することと
を含む、請求項1に記載の方法。 - 前記疾患が、自己免疫糖尿病、例えば、1型真性糖尿病である、請求項1に記載の方法。
- HLA DR3−DQ2ハプロタイプを有し、任意に、GADAを最初に示す個体が、少なくともGAD自己抗原による処置に供される、請求項1〜3のいずれか一項に記載の方法。
- HLA DR3/4−DQ2/8遺伝子型を有する個体が、同じ製剤または別々の製剤中のGAD自己抗原およびインスリン自己抗原の両方による処置に供される、請求項1〜3のいずれか一項に記載の方法。
- DR4−DQ8ハプロタイプを有するが、DR3−DQ2ハプロタイプを有さず、任意に、インスリン自己抗体を最初に示す個体が、少なくともインスリン自己抗原による処置に供される、請求項1〜3のいずれか一項に記載の方法。
- DR4−DQ8を有するが、DR3−DQ2ハプロタイプを有しない個体が、アラム単独による処置に供される、請求項1〜3のいずれか一項に記載の方法。
- HLA DR8/4−DQ4/8ハプロ遺伝子型を有し、任意に、インスリン自己抗体を最初に示す個体が、少なくともインスリン自己抗原による処置に供される、請求項1〜3のいずれか一項に記載の方法。
- GAD抗原の投与が、皮下、皮内またはリンパ内のうちの1つである、請求項1〜8のいずれか一項に記載の方法。
- GAD抗原が、アラムと共に製剤化される、請求項1〜9のいずれか一項に記載の方法。
- インスリン自己抗原の投与が、経口、舌下、筋内、皮内またはリンパ内である、請求項1〜8のいずれか一項に記載の方法。
- インスリン抗原が、アラムと共に、または生理食塩水中で製剤化される、請求項1〜9または11に記載の方法。
- アラム単独の投与が、皮下、皮内またはリンパ内である、請求項1〜8のいずれか一項に記載の方法。
- 請求項1〜13のいずれか一項に記載の方法における自己抗原としての使用のためのGAD。
- 請求項1〜13のいずれか一項に記載の方法における自己抗原としての使用のためのインスリン。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2023099313A JP2023116726A (ja) | 2017-09-08 | 2023-06-16 | 糖尿病の処置および予防における遺伝子型層別化 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE1751094-2 | 2017-09-08 | ||
SE1751094 | 2017-09-08 | ||
PCT/SE2018/050904 WO2019050465A1 (en) | 2017-09-08 | 2018-09-10 | STRATIFICATION OF GENOTYPE IN THE TREATMENT AND PREVENTION OF DIABETES |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2023099313A Division JP2023116726A (ja) | 2017-09-08 | 2023-06-16 | 糖尿病の処置および予防における遺伝子型層別化 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2020533306A true JP2020533306A (ja) | 2020-11-19 |
JP2020533306A5 JP2020533306A5 (ja) | 2021-10-14 |
JP7337780B2 JP7337780B2 (ja) | 2023-09-04 |
Family
ID=65634471
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020513715A Active JP7337780B2 (ja) | 2017-09-08 | 2018-09-10 | 糖尿病の処置および予防における遺伝子型層別化 |
JP2023099313A Pending JP2023116726A (ja) | 2017-09-08 | 2023-06-16 | 糖尿病の処置および予防における遺伝子型層別化 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2023099313A Pending JP2023116726A (ja) | 2017-09-08 | 2023-06-16 | 糖尿病の処置および予防における遺伝子型層別化 |
Country Status (20)
Country | Link |
---|---|
US (1) | US20210077587A1 (ja) |
EP (2) | EP3954384A1 (ja) |
JP (2) | JP7337780B2 (ja) |
KR (2) | KR102607713B1 (ja) |
CN (1) | CN111372602A (ja) |
CA (1) | CA3074264A1 (ja) |
CY (1) | CY1124881T1 (ja) |
DK (1) | DK3678692T3 (ja) |
EA (1) | EA202090673A1 (ja) |
ES (1) | ES2902075T3 (ja) |
HR (1) | HRP20211989T1 (ja) |
HU (1) | HUE057216T2 (ja) |
IL (1) | IL273016A (ja) |
LT (1) | LT3678692T (ja) |
MX (1) | MX2020002462A (ja) |
PL (1) | PL3678692T3 (ja) |
PT (1) | PT3678692T (ja) |
RS (1) | RS62725B1 (ja) |
SI (1) | SI3678692T1 (ja) |
WO (1) | WO2019050465A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3873601A4 (en) * | 2019-05-14 | 2022-03-23 | Provention Bio, Inc. | METHODS AND COMPOSITIONS FOR THE PREVENTION OF TYPE 1 DIABETES |
KR20230031981A (ko) * | 2019-05-14 | 2023-03-07 | 프로벤션 바이오, 인코포레이티드 | 제1형 당뇨병을 예방하기 위한 방법 및 조성물 |
GB201913408D0 (en) * | 2019-09-17 | 2019-10-30 | King S College London | Proinsulin peptides for type 1 diabetes |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017516870A (ja) * | 2014-06-04 | 2017-06-22 | ダイアミド・メディカル・アクチボラゲットDiamyd Medical Ab | 抗原ベース療法薬の新規な併用 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FI923719A0 (fi) * | 1992-08-19 | 1992-08-19 | Jaakko Tuomilehto | Detektering av susceptibilitet foer diabetes. |
EP1755631A2 (en) | 2004-03-03 | 2007-02-28 | Diamyd Medical AB | Immunomodulation by a therapeutic medication intended for treatment of diabetes and prevention of autoimmune diabetes |
-
2018
- 2018-09-10 US US16/644,461 patent/US20210077587A1/en active Pending
- 2018-09-10 KR KR1020207009990A patent/KR102607713B1/ko active IP Right Grant
- 2018-09-10 DK DK18854165.0T patent/DK3678692T3/da active
- 2018-09-10 EP EP21195581.0A patent/EP3954384A1/en active Pending
- 2018-09-10 RS RS20211551A patent/RS62725B1/sr unknown
- 2018-09-10 PL PL18854165T patent/PL3678692T3/pl unknown
- 2018-09-10 EA EA202090673A patent/EA202090673A1/ru unknown
- 2018-09-10 CA CA3074264A patent/CA3074264A1/en active Pending
- 2018-09-10 KR KR1020237040525A patent/KR20230167442A/ko not_active Application Discontinuation
- 2018-09-10 EP EP18854165.0A patent/EP3678692B1/en active Active
- 2018-09-10 JP JP2020513715A patent/JP7337780B2/ja active Active
- 2018-09-10 SI SI201830501T patent/SI3678692T1/sl unknown
- 2018-09-10 HR HRP20211989TT patent/HRP20211989T1/hr unknown
- 2018-09-10 PT PT188541650T patent/PT3678692T/pt unknown
- 2018-09-10 ES ES18854165T patent/ES2902075T3/es active Active
- 2018-09-10 MX MX2020002462A patent/MX2020002462A/es unknown
- 2018-09-10 HU HUE18854165A patent/HUE057216T2/hu unknown
- 2018-09-10 CN CN201880071819.3A patent/CN111372602A/zh active Pending
- 2018-09-10 LT LTEPPCT/SE2018/050904T patent/LT3678692T/lt unknown
- 2018-09-10 WO PCT/SE2018/050904 patent/WO2019050465A1/en unknown
-
2020
- 2020-03-03 IL IL273016A patent/IL273016A/en unknown
-
2021
- 2021-12-23 CY CY20211101133T patent/CY1124881T1/el unknown
-
2023
- 2023-06-16 JP JP2023099313A patent/JP2023116726A/ja active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017516870A (ja) * | 2014-06-04 | 2017-06-22 | ダイアミド・メディカル・アクチボラゲットDiamyd Medical Ab | 抗原ベース療法薬の新規な併用 |
Non-Patent Citations (3)
Title |
---|
LUDVIGSSON, J. ET AL., DIABETES METAB RES REV, vol. 30, JPN6022040637, 2014, pages 405 - 414, ISSN: 0004888096 * |
NILSSON, C. ET AL., PEDIATR DIABETES, vol. Vol. 12, Suppl. 15, JPN6022040635, 2011, pages 114, ISSN: 0004888095 * |
POCIOT, F. ET AL., LANCET, vol. 387, JPN6022040638, 2016, pages 2331 - 2339, ISSN: 0004888097 * |
Also Published As
Publication number | Publication date |
---|---|
CY1124881T1 (el) | 2022-11-25 |
EP3954384A1 (en) | 2022-02-16 |
KR102607713B1 (ko) | 2023-11-29 |
US20210077587A1 (en) | 2021-03-18 |
EP3678692B1 (en) | 2021-10-20 |
JP2023116726A (ja) | 2023-08-22 |
KR20200051737A (ko) | 2020-05-13 |
ES2902075T3 (es) | 2022-03-24 |
EA202090673A1 (ru) | 2020-06-23 |
MX2020002462A (es) | 2020-09-22 |
PT3678692T (pt) | 2021-12-29 |
EP3678692A4 (en) | 2021-06-02 |
WO2019050465A1 (en) | 2019-03-14 |
PL3678692T3 (pl) | 2022-02-28 |
EP3678692A1 (en) | 2020-07-15 |
CA3074264A1 (en) | 2019-03-14 |
DK3678692T3 (da) | 2022-01-03 |
IL273016A (en) | 2020-04-30 |
SI3678692T1 (sl) | 2022-04-29 |
KR20230167442A (ko) | 2023-12-08 |
CN111372602A (zh) | 2020-07-03 |
RS62725B1 (sr) | 2022-01-31 |
HUE057216T2 (hu) | 2022-04-28 |
LT3678692T (lt) | 2022-01-10 |
JP7337780B2 (ja) | 2023-09-04 |
HRP20211989T1 (hr) | 2022-03-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Ziegler et al. | Primary prevention of beta-cell autoimmunity and type 1 diabetes–The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) perspectives | |
Ippoliti et al. | Immunomodulation during sublingual therapy in allergic children | |
Näntö-Salonen et al. | Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial | |
JP2023116726A (ja) | 糖尿病の処置および予防における遺伝子型層別化 | |
RU2702632C2 (ru) | Новые комбинации для антигенной терапии | |
Assfalg et al. | Oral insulin immunotherapy in children at risk for type 1 diabetes in a randomised controlled trial | |
US20090092637A1 (en) | Medicaments and methods to treat autoimmune disease and cancer | |
Schloot et al. | DiaPep277® and immune intervention for treatment of type 1 diabetes | |
JP2010525049A5 (ja) | ||
Sheng et al. | Immune response and safety of heterologous ChAdOx1-nCoV-19/mRNA-1273 vaccination compared with homologous ChAdOx1-nCoV-19 or homologous mRNA-1273 vaccination | |
Aydoğan et al. | Type 1 diabetes mellitus following SARS-CoV-2 mRNA vaccination | |
Niiya et al. | Impaired dendritic cell function resulting from chronic undernutrition disrupts the antigen-specific immune response in mice | |
Hansen et al. | Early life interventions to prevent allergy in the offspring: the role of maternal immunization and postnatal mucosal allergen exposure | |
EA043223B1 (ru) | Стратификация генотипа при лечении и профилактике диабета | |
CN102755633A (zh) | 人重组蛋白pdcd5在治疗自身免疫病中的应用 | |
Martens et al. | Preventing type 1 diabetes in late-stage pre-diabetic NOD mice with insulin: A central role for alum as adjuvant | |
JP4463525B2 (ja) | 減感作療法用剤 | |
JP7413254B2 (ja) | 改善された免疫療法 | |
Reddy et al. | Temporal relationship between immune cell influx and the expression of inducible nitric oxide synthase, interleukin-4 and interferon-γ in pancreatic islets of NOD mice following adoptive transfer of diabetic spleen cells | |
McCusker | Egg Desensitization and induction of tolerance in Children Principal Investigator: Moshe Ben-Shoshan MD McGill University Health Center Sub-Investigators: Bruce Mazer MD McGill University Health Center | |
Al-Bayati | Analysis of causes that led to the development of vitiligo in Jeanett’s case with recommendations for clinical tests and treatments | |
Nambam et al. | Immune interventions for type 1 diabetes mellitus | |
Li et al. | GPR41 deficiency aggravates type 1 diabetes in streptozotocin-treated mice by promoting dendritic cell maturation | |
Park et al. | A 9-year-old boy with chronic urticaria and progressive spondyloarthritis. | |
Assfalg et al. | Immune outcomes and safety of high-dose oral insulin as a primary prevention immunotherapy in young autoantibody-negative children at high genetic risk for type 1 diabetes |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210831 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20210831 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20221004 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20221216 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20230228 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230616 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20230616 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20230705 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20230725 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20230823 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7337780 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |