ES2281918T3 - Metodos para diagnosticar glaucoma y descubrir farmacos antiglaucoma. - Google Patents
Metodos para diagnosticar glaucoma y descubrir farmacos antiglaucoma. Download PDFInfo
- Publication number
- ES2281918T3 ES2281918T3 ES97947569T ES97947569T ES2281918T3 ES 2281918 T3 ES2281918 T3 ES 2281918T3 ES 97947569 T ES97947569 T ES 97947569T ES 97947569 T ES97947569 T ES 97947569T ES 2281918 T3 ES2281918 T3 ES 2281918T3
- Authority
- ES
- Spain
- Prior art keywords
- glaucoma
- grβ
- expression
- gene
- comprises detecting
- 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.)
- Expired - Lifetime
Links
- 208000010412 Glaucoma Diseases 0.000 title claims abstract description 23
- 238000000034 method Methods 0.000 title claims abstract description 15
- 230000001384 anti-glaucoma Effects 0.000 title description 2
- 101150047053 GR gene Proteins 0.000 claims description 5
- 108700028369 Alleles Proteins 0.000 claims description 4
- 101000926939 Homo sapiens Glucocorticoid receptor Proteins 0.000 claims description 4
- 230000001594 aberrant effect Effects 0.000 claims description 4
- 102000054765 polymorphisms of proteins Human genes 0.000 claims description 4
- 230000007547 defect Effects 0.000 claims description 3
- 238000007894 restriction fragment length polymorphism technique Methods 0.000 claims description 3
- 238000012360 testing method Methods 0.000 claims description 3
- 101000829171 Hypocrea virens (strain Gv29-8 / FGSC 10586) Effector TSP1 Proteins 0.000 claims description 2
- 108091034117 Oligonucleotide Proteins 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000011544 gradient gel Substances 0.000 claims description 2
- 238000009396 hybridization Methods 0.000 claims description 2
- 230000002068 genetic effect Effects 0.000 claims 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims 1
- 239000012634 fragment Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 5
- 238000001514 detection method Methods 0.000 abstract description 3
- 238000003745 diagnosis Methods 0.000 abstract description 3
- 238000012216 screening Methods 0.000 abstract description 2
- 229940124597 therapeutic agent Drugs 0.000 abstract description 2
- 102000003676 Glucocorticoid Receptors Human genes 0.000 description 19
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 19
- 239000003862 glucocorticoid Substances 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 229940037128 systemic glucocorticoids Drugs 0.000 description 4
- 238000003556 assay Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000004410 intraocular pressure Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 2
- 206010030043 Ocular hypertension Diseases 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 241000282412 Homo Species 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 238000000670 ligand binding assay Methods 0.000 description 1
- 230000003547 miosis Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001585 trabecular meshwork Anatomy 0.000 description 1
Classifications
-
- 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
- C12Q2600/156—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
- C12Q2600/158—Expression markers
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Analytical Chemistry (AREA)
- Wood Science & Technology (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Eye Examination Apparatus (AREA)
Abstract
LA PRESENTE INVENCION SE REFIERE A UNOS PROCEDIMIENTOS QUE PERMITEN EL DIAGNOSTICO DEL GLAUCOMA Y EL CRIBADO DE LOS AGENTES TERAPEUTICOS EN FUNCION DE SU UTILIDAD EN EL TRATAMIENTO DEL GLAUCOMA, LOS CUALES SE BASAN EN LA DETECCION DE LA EXPRESION ABERRANTE DEL RECEPTOR DE GLUCOCORTICOIDE BETA (GRBETA).
Description
Métodos para diagnosticar glaucoma y descubrir
fármacos antiglaucoma.
El glaucoma se diagnostica generalmente
monitorizando la pérdida de campo visual de un paciente, los cambios
en la apariencia de su disco óptico, y su presión intraocular. El
glaucoma se trata actualmente usando una o más de entre tres
estrategias para disminuir la presión intraocular elevada asociada
con la enfermedad: con fármacos (tales como
beta-bloqueadores, inhibidores de la anhidrasa
carbónica, y mióticos), con trabeculoplastia con láser, y/o con
cirugía filtrante del glaucoma. Todas estas terapias disminuyen
indirectamente la presión intraocular pero no tratan el proceso de
enfermedad subyacente que tiene lugar en la red trabecular. Sería
ventajoso ser capaces de diagnosticar el glaucoma antes de que el
paciente comience a experimentar una pérdida en su campo visual y
un deterioro de su disco óptico.
Existe un gran conjunto de pruebas que sugieren
que los glucocorticoides están implicados en la generación de la
hipertensión ocular y el glaucoma. Véase Clark, A. F., Journal of
Glaucoma, "Steroids, Ocular Hypertension, and Glaucoma",
4:354-369, 1995. Varios investigadores han
demostrado que la red trabecular humana (TM, del inglés
"trabecular meshwork") contiene el receptor de glucocorticoides
clásico (GR\alpha). Véanse Weinreb, et al., Invest.
Ophthalmol. Vis. Sci., "Detection of Glucocorticoid Receptors
in Cultured Human Trabecular Cells", 21:3,
403-407, 1981, y Hernández, et al.,
Invest. Ophthalmol. Vis. Sci., "Glucocorticoid Target
Cells in Human Outflow Pathway: Autopsy and Surgical Specimens,"
24:1612-1616, 1983. Recientemente, se descubrió la
expresión de una forma cortada y empalmada alternativamente del
receptor de glucocorticoides humano (GR\beta) en tejidos y
células no oculares. Véanse Bamberger, et al., The Journal of
Clinical Investigation, "Glucocorticoid Receptor \beta, a
Potential Endogenous Inhibitor of Glucocorticoid Action in
Humans", 95:2435-2441, 1995, y Oakley, et
al., The Journal of Biological Chemistry, "The Human
Glucocorticoid Receptor \beta Isoform,"
271:16,9550-9559, 1996. Esta forma cortada y
empalmada alternativamente del receptor de glucocorticoides (GR) se
expresa como una proteína que ya no se une a glucocorticoides, pero
es capaz de interferir con la forma activada del receptor de
glucocorticoides normal y bloquear o alterar las funciones
fisiológicas del receptor de glucocorticoides.
La presente invención está dirigida a métodos
para diagnosticar glaucoma sometiendo a ensayo a una persona para
detectar la expresión aberrante de GR\beta. También se establecen
métodos para el escrutinio de agentes terapéuticos útiles para
tratar glaucoma.
Sorprendentemente, se ha encontrado que líneas
celulares cultivadas de la red trabecular humana derivadas de
donantes glaucomatosos expresan el mRNA tanto para una forma de
corte y empalme alternativo del receptor de glucocorticoides humano
(GR\beta), como el receptor de glucocorticoides normal
(GR\alpha), mientras que las líneas celulares de TM normal
expresan sólo mRNA para GR\alpha. Se cree que la presión
intraocular elevada asociada con el glaucoma primario de ángulo
abierto puede deberse a la expresión aberrante de GR\beta en la
red trabecular. Por lo tanto, la determinación de que un individuo
expresa de modo anormal GR\beta en su red trabecular u otros
tejidos puede conducir a un diagnóstico de glaucoma. Además, este
descubrimiento puede usarse para determinar si los agentes tienen
valor terapéutico en el tratamiento del glaucoma determinando si
interactúan con GR\beta o alteran la expresión de GR\beta. Esto
puede hacerse usando ensayos de unión a ligandos o ensayos
funcionales de GR\beta.
El diagnóstico de la expresión aberrante de
GR\beta o defectos en el gen GR que codifica GR\beta puede
hacerse usando procedimientos bien conocidos por los expertos en la
técnica. Véase Caskey, C.T., J.A.M.A., "Molecular
Medicine: A Spin-off From the Helix", 269:15,
1986-1992, 1993. Por ejemplo, los sujetos podrían
someterse a escrutinio para determinar la presencia de un defecto
genético en GR\beta analizando el DNA derivado de leucocitos de
sangre periférica. Los tipos de análisis de DNA podrían incluir,
pero no estarían limitados a ellos: polimorfismos en la longitud de
los fragmentos de restricción (RFLP, del inglés "restriction
fragment length polymorphisms"), polimorfismos en la conformación
de cadenas sencillas (SSCP, del inglés
"single-stranded conformation polymorphisms"),
reacción en cadena de la polimerasa (PCR, del inglés "polymerase
chain reaction"), geles en gradiente desnaturalizante, ensayo de
ligación de oligonucleótidos específico de alelo, y ensayo de
hibridación específico de alelo. Además, la red trabecular, u otras
células relevantes de los sujetos podrían analizarse para detectar
la expresión de GR\beta por varias técnicas tales como la reacción
en cadena de la polimerasa de trascripción inversa
(RT-PCR, del inglés "
reverse-transcription polymerase chain
reaction"), inmunoensayos, ensayos funcionales de GR, etc.
El documento WO 96/14411 describe un método para
diagnosticar glaucoma en un paciente que comprende determinar si la
cantidad de una proteína de respuesta a glucocorticoides inducida
por la red trabecular presente en la red trabecular del ojo de un
paciente excede la cantidad de esa proteína de respuesta a
glucocorticoides inducida por la red trabecular presente en la red
trabecular del ojo de un individuo que no sufre de glaucoma, en el
que la detección de una cantidad excesiva de la proteína de
respuesta a glucocorticoides inducida en la red trabecular es
indicativa de glaucoma.
Claims (5)
1. Un método para diagnosticar glaucoma que
comprende detectar la expresión de la forma de corte y empalme
alternativa del receptor de glucocorticoides humano (GR\beta)
aberrante o defectos en un gen GR que codifica GR\beta.
2. El método de la Reivindicación 1 en el que
los defectos en un gen GR se detectan por un método seleccionado
del grupo de ensayos que consiste en: polimorfismos en la longitud
de los fragmentos de restricción (RFLP), polimorfismos en la
conformación de cadenas sencillas (SSCP), reacción en cadena de la
polimerasa (PCR), gel en gradiente desnaturalizante, ligación de
oligonucleótidos específica de alelo, e hibridación específica de
alelo.
3. Un método para diagnosticar glaucoma, que
comprende detectar cambios genéticos en el gen GR que conducen a
una expresión alterada de GR\beta.
4. Un método para diagnosticar glaucoma, que
comprende detectar cambios genéticos fuera del gen GR que conducen
a una expresión alterada de GR\beta.
5. Un método para determinar si un agente es
útil para tratar glaucoma determinando si interactúa con GR\beta
o altera la expresión de GR\beta.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3322796P | 1996-12-05 | 1996-12-05 | |
| US33227P | 1996-12-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2281918T3 true ES2281918T3 (es) | 2007-10-01 |
Family
ID=21869226
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES97947569T Expired - Lifetime ES2281918T3 (es) | 1996-12-05 | 1997-11-14 | Metodos para diagnosticar glaucoma y descubrir farmacos antiglaucoma. |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP0943014B1 (es) |
| JP (1) | JP2001505434A (es) |
| AT (1) | ATE354671T1 (es) |
| AU (1) | AU728438B2 (es) |
| CA (1) | CA2274244C (es) |
| DE (1) | DE69737393T2 (es) |
| DK (1) | DK0943014T3 (es) |
| ES (1) | ES2281918T3 (es) |
| PT (1) | PT943014E (es) |
| WO (1) | WO1998024932A1 (es) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7220546B2 (en) | 1996-12-05 | 2007-05-22 | Alcon Manufacturing, Ltd. | Methods for diagnosing glaucoma and discovering anti-glaucoma drugs |
| CA2401775A1 (en) * | 2000-02-29 | 2001-09-07 | Abbot F. Clark | Diagnostics and therapeutics for glaucoma |
| CA2463143A1 (en) * | 2001-10-31 | 2003-07-10 | Alcon, Inc. | Bone morphogenic proteins (bmp), bmp receptors and bmp binding proteins and their use in the diagnosis and treatment of glaucoma |
| AU2002238800A1 (en) * | 2002-03-01 | 2003-09-16 | Flammer, Josef | Diagnostic method for glaucoma |
| US8182990B2 (en) * | 2004-03-18 | 2012-05-22 | Rusk Intellectual Reserve Ag | Method for diagnosing or predicting susceptibility to optic neuropathy |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5606043A (en) * | 1994-11-03 | 1997-02-25 | The Regents Of The University Of California | Methods for the diagnosis of glaucoma |
| FR2733251B1 (fr) * | 1995-04-18 | 1997-07-04 | Inst Nat Sante Rech Med | Depistage du glaucome juvenile |
-
1997
- 1997-11-14 PT PT97947569T patent/PT943014E/pt unknown
- 1997-11-14 DE DE69737393T patent/DE69737393T2/de not_active Expired - Lifetime
- 1997-11-14 AU AU52617/98A patent/AU728438B2/en not_active Ceased
- 1997-11-14 ES ES97947569T patent/ES2281918T3/es not_active Expired - Lifetime
- 1997-11-14 CA CA002274244A patent/CA2274244C/en not_active Expired - Fee Related
- 1997-11-14 WO PCT/US1997/021054 patent/WO1998024932A1/en not_active Ceased
- 1997-11-14 EP EP97947569A patent/EP0943014B1/en not_active Expired - Lifetime
- 1997-11-14 DK DK97947569T patent/DK0943014T3/da active
- 1997-11-14 AT AT97947569T patent/ATE354671T1/de active
- 1997-11-14 JP JP52560698A patent/JP2001505434A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DE69737393D1 (de) | 2007-04-05 |
| PT943014E (pt) | 2007-03-30 |
| JP2001505434A (ja) | 2001-04-24 |
| WO1998024932A1 (en) | 1998-06-11 |
| EP0943014A1 (en) | 1999-09-22 |
| AU728438B2 (en) | 2001-01-11 |
| CA2274244A1 (en) | 1998-06-11 |
| CA2274244C (en) | 2008-11-04 |
| DE69737393T2 (de) | 2007-06-14 |
| ATE354671T1 (de) | 2007-03-15 |
| AU5261798A (en) | 1998-06-29 |
| DK0943014T3 (da) | 2007-05-07 |
| EP0943014B1 (en) | 2007-02-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Shimizu et al. | Age-dependent prevalence of mutations at the GLC1A locus in primary open-angle glaucoma | |
| Friedl et al. | Familial adenomatous polyposis: experience from a study of 1164 unrelated german polyposis patients | |
| Dighiero et al. | Histologic phenotype–genotype correlation of corneal dystrophies associated with eight distinct mutations in the TGFBI gene | |
| JP4255382B2 (ja) | 骨形成タンパク質（ｂｍｐ）、ｂｍｐレセプターおよびｂｍｐ結合タンパク質ならびに緑内障の診断および処置におけるそれらの使用 | |
| Wutz et al. | Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling in mouse retina | |
| Hitchcock et al. | A review of the genetics of intracranial berry aneurysms and implications for genetic counseling | |
| Dighiero et al. | A new mutation (A546T) of the βig-h3 gene responsible for a French lattice corneal dystrophy type IIIA | |
| Ellies et al. | Clinical outcome of eight BIGH3-linked corneal dystrophies | |
| JP2003506016A (ja) | 動脈壁破裂障害のための診断剤および治療剤 | |
| Ichikawa et al. | A case of solitary subependymal giant cell astrocytoma: two somatic hits of TSC2 in the tumor, without evidence of somatic mosaicism | |
| Vincent et al. | Screening the visual system homeobox 1 gene in keratoconus and posterior polymorphous dystrophy cohorts identifies a novel variant | |
| Jang et al. | Posterior polymorphous corneal dystrophy 3 is associated with agenesis and hypoplasia of the corpus callosum | |
| Pasini et al. | RET mutation profile and variable clinical manifestations in a family with multiple endocrine neoplasia type 2A and Hirschsprung's disease | |
| EP1137947B1 (en) | Method for determining asthma susceptibility | |
| ES2478624T3 (es) | Métodos para el diagnóstico y el tratamiento de la epilepsia | |
| EP0943014B1 (en) | Methods for diagnosing glaucoma and discovering anti-glaucoma drugs | |
| US20110104687A1 (en) | Methods and Kits for Detecting Congenital Stationary Night Blindness and Selecting Different Coat Patterns | |
| Sitorus et al. | Analysis of three genes in Leber congenital amaurosis in Indonesian patients | |
| Fuse et al. | Molecular genetic analysis of ABCR gene in Japanese dry form age-related macular degeneration | |
| US20020042050A1 (en) | Methods for diagnosing glaucoma and discovering anti-glaucoma drugs | |
| Colligris et al. | Recent patents and developments in glaucoma biomarkers | |
| US7220546B2 (en) | Methods for diagnosing glaucoma and discovering anti-glaucoma drugs | |
| Avisar et al. | The novel Y371D myocilin mutation causes an aggressive form of juvenile open-angle glaucoma in a Caucasian family from the Middle-East | |
| Mizutani et al. | ABCC6 mutation in patients with angioid streaks | |
| Haim et al. | Novel rhodopsin mutation (M216R) in a Danish family with autosomal dominant retinitis pigmentosa |