CA2454073A1 - Mutations in ion channels - Google Patents

Mutations in ion channels Download PDF

Info

Publication number
CA2454073A1
CA2454073A1 CA002454073A CA2454073A CA2454073A1 CA 2454073 A1 CA2454073 A1 CA 2454073A1 CA 002454073 A CA002454073 A CA 002454073A CA 2454073 A CA2454073 A CA 2454073A CA 2454073 A1 CA2454073 A1 CA 2454073A1
Authority
CA
Canada
Prior art keywords
disease
ion channel
nucleic acid
blindness
polypeptide
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
Application number
CA002454073A
Other languages
French (fr)
Other versions
CA2454073C (en
Inventor
John Charles Mulley
Louise Anne Harkin
Leanne Michelle Dibbens
Hilary Anne Phillips
Sarah Elizabeth Heron
Samuel Frank Berkovic
Ingrid Eileen Scheffer
Robyn Wallace
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bionomics Ltd
Original Assignee
Individual
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
Priority claimed from AUPR6452A external-priority patent/AUPR645201A0/en
Priority claimed from AUPS0910A external-priority patent/AUPS091002A0/en
Priority claimed from AUPS2292A external-priority patent/AUPS229202A0/en
Application filed by Individual filed Critical Individual
Publication of CA2454073A1 publication Critical patent/CA2454073A1/en
Application granted granted Critical
Publication of CA2454073C publication Critical patent/CA2454073C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • 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

Abstract

A method of identifying a subject predisposed to a disorder associated with ion channel dysfunction, comprising ascertaining whether at least one of the genes encoding ion channel subunits in said subject has undergone a mutation event such that a cDNA derived from said subject has the sequence set forth in one of SEQ ID NOS: 1-134.

Claims (95)

1. A method of identifying a subject predisposed to a disorder associated with ion channel dysfunction, comprising ascertaining whether at least one of the genes encoding ion channel subunits in said subject has undergone a mutation event such that a cDNA derived from said subject has the sequence set forth in one of SEQ ID
NOS: 1-134.
2. A method as claimed in claim 1, wherein said mutation event disrupts the functioning of an assembled ion channel so as to produce an epilepsy phenotype in said subject.
3. A method as claimed in claim 1, wherein said mutation event disrupts the functioning of an assembled ion channel so as to produce one or more disorders associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness and total colour-blindness in said subject.
4. A method as claimed in claim 1, wherein said mutation event disrupts the functioning of an assembled ion channel so as to produce an epilepsy phenotype when expressed in combination with one or more additional mutations or variations in said ion channel subunit genes.
5. A method as claimed in claim 1, wherein said mutation event disrupts the functioning of an assembled ion channel so as to produce one or more disorders associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness and total colour-blindness, when expressed In cOmbi.nata.On with one or more additional mutations or variations in said ion channel subunit genes.
6. An isolated nucleic acid molecule encoding a mutant or variant ion channel subunit wherein a mutation event has occurred such that a cDNA derived therefrom has the sequence set forth in one of SEQ ID NOS: 1-134.
7. An isolated nucleic acid molecule encoding a mutant or variant ion channel subunit as claimed in claim 6, wherein said mutation event disrupts the functioning of an assembled ion channel so as to produce an epilepsy phenotype.
8. An isolated nucleic acid molecule encoding a mutant or variant ion channel subunit as claimed in claim 6, wherein said mutation event disrupts the functioning of an assembled ion channel so as to produce one or more disorders associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness and total colour-blindness.
9. An isolated nucleic acid molecule encoding a mutant or variant ion channel subunit as claimed in claim 6, wherein said mutation event disrupts the functioning of an assembled ion channel so as to produce an epilepsy phenotype when expressed in combination with one or more additional mutations or variations in said ion channel subunit genes.
10. An isolated nucleic acid molecule encoding a mutant or variant ion channel subunit as claimed in claim 6, wherein said mutation event disrupts the functioning of an assembled ion channel so as to produce one or more disorders associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Banter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness and total colour-blindness, when expressed in combination with one or more additional mutations or variations in said ion channel subunit genes.
11. An isolated nucleic acid molecule comprising any one of the nucleotide sequences set forth in SEQ ID NOS: 1-134.
12. An isolated nucleic acid molecule consisting of any one of the nucleotide sequences set forth in SEQ ID NOS:
1-134.
13. An isolated polypeptide, said polypeptide being a mutant or variant ion channel subunit wherein a mutation event has occurred such that the polypeptide has the amino acid sequence set forth in one of SEQ ID NOS: 135-173.
14. An isolated polypeptide, said polypeptide being a mutant or variant ion channel subunit as claimed in claim 13, wherein said mutation event disrupts the functioning of an assembled ion channel so as to produce an epilepsy phenotype.
15. An isolated polypeptide, said polypeptide being a mutant or variant ion channel subunit as claimed in claim 13, wherein said mutation event disrupts the functioning of an assembled ion channel so as to produce one or more disorders associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness and total colour-blindness.
16. An isolated polypeptide, said polypeptide being a mutant or variant ion channel subunit as claimed in claim 13, wherein said mutation event disrupts the functioning of an assembled ion channel so as to produce an epilepsy phenotype when expressed in combination with one or more additional mutations or variations in said ion channel subunit genes.
17. An isolated polypeptide, said polypeptide being a mutant or variant ion channel subunit as claimed in claim 13, wherein said mutation event disrupts the functioning of an assembled ion channel so as to produce one or more disorders associated with ion channel dysfunction, including but riot restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness and total colour-blindness, when expressed in combination with one or more additional mutations or variations in said ion channel subunit genes.
18. An isolated polypeptide comprising any one of the amino acid sequences set forth in SEQ ID NOS: 135-173.
19. An isolated polypeptide consisting of any one of the amino acid sequences set forth in SEQ ID NOS: 135-173.
20. An isolated polypeptide complex, said polypeptide complex being an assembled mammalian ion channel including an ion channel subunit comprising a polypeptide as defined in any one of claims 13 to 19.
21. An expression vector comprising a nucleic acid molecule as defined in any one of claims 6 to 12.
22. A cell transformed with at least one expression vector as defined in claim 21.
23. A cell as claimed in claim 21 transformed with two or more expression vectors.
24. A cell comprising at least one ion channel type, wherein the or each ion channel type incorporates at least one mutant polypeptide as defined in any one claims 13 to 19.
25. A cell as claimed in claim 24 comprising ion channels that incorporate two or more mutant polypeptides.
26. A cell as claimed in claim 24 comprising two or more ion channel types each incorporating one or more mutant polypeptide.
27. A method of preparing a polypeptide, comprising the steps of:
(1) culturing cells as claimed in any one of claims 22 to 26 under conditions effective for polypeptide production; and (2) harvesting the polypeptide.
28. A polypeptide prepared by the method of claim 27.
29. An antibody which is immunologically reactive with an isolated polypeptide as claimed in any one of claims 13 to 19 or claim 28, or an isolated polypeptide complex as claimed in claim 20.
30. An antibody as claimed in claim 29 which is selected from the group consisting of a monoclonal antibody, a humanised antibody, a chimeric antibody or an antibody fragment including a Fab fragment, (Fab')2 fragment, Fv fragment, single chain antibodies and single domain antibodies.
31. A method of treating epilepsy comprising administering an antibody as claimed in either one of claims 29 or 30 to a subject in need of such treatment.
32. The use of an antibody, as claimed in either one of claims 29 or 30, in the manufacture of a medicament for the treatment of epilepsy.
33. A method of treating a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness, comprising administering an antibody as claimed in either one of claims 29 or 30 to a subject in need of such treatment.
34. The use of an antibody, as claimed in either one of claims 29 or 30, in the manufacture of a medicament for the treatment of a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or- total colour-blindness.
35. A method of treating epilepsy comprising administering a selective agonist, antagonist or modulator of an ion channel when it has undergone a mutation event or combination of events as defined in any one of claims 1 to 10 or claims 13 to 17 to a subject in need of such treatment.
36. The use of a selective agonist, antagonist or modulator of an ion channel when it has undergone a mutation event as defined in any one of claims 1 to 10 or claims 13 to 17 in the manufacture of a medicament for the treatment of epilepsy.
37. A method of treating a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness, comprising administering a selective agonist, antagonist or modulator of an ion channel when it has undergone a mutation event or combination of events as defined in any one of claims 1 to 10 or claims 13 to 17 to a subject in need of such treatment.
38. The use of a selective agonist, antagonist or modulator of an ion channel when it has undergone a mutation event as claimed in any one of claims 1 to 10 or claims 13 to 17 in the manufacture of a medicament for the treatment of a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness.
39. A method of treating epilepsy comprising administering an isolated DNA molecule which is the complement (antisense) of a nucleic acid molecule as claimed in any one of claims 6 to 12 and which encodes an RNA molecule that hybridizes with the mRNA encoded by a nucleic acid molecule as claimed in any one of claims 6 to 12, to a subject in need of such treatment.
40. The use of a DNA molecule which is the complement of a nucleic acid molecule as claimed in any one of claims 6 to 12 and which encodes an RNA molecule that hybridizes with the mRNA encoded by a nucleic acid molecule as claimed in any one of claims 6 to 12, in the manufacture of a medicament for the treatment of epilepsy.
41. A method of treating a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness, comprising administering an isolated DNA molecule which is the complement (antisense) of a nucleic acid molecule as claimed in any one of claims 6 to 12 and which encodes an RNA molecule that hybridizes with the mRNA encoded by a nucleic acid molecule as claimed in any one of claims 6 to 12, to a subject in need of such treatment.
42. The use of a DNA molecule which is the complement of a nucleic acid molecule as claimed in any one of claims 6 to 12 and which encodes an RNA molecule that hybridizes with the mRNA encoded by a nucleic acid molecule as claimed in any one of claims 6 to 12, in the manufacture of a medicament for the treatment of a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent s disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness.
43. A method of treating epilepsy comprising administering an antibody, as claimed in either one of claims 29 or 30, administration of an agonist, antagonist or modulator of an ion channel when it has undergone a mutation event or combination of events as defined in any one of claims 1 to 10 or claims 13 to 17, or administration of a DNA molecule which is the complement of a nucleic acid molecule as claimed in any one of claims 6 to 12 and which encodes an RNA molecule that hybridizes with the mRNA encoded by a nucleic acid molecule as claimed in any one of claims 6 to 12, in combination with administration of the wild-type ion channel subunit, to a subject in need of such treatment.
44. The use of an antibody, as claimed in claims 29 or 30, use of an agonist, antagonist or modulator of an ion channel when it has undergone a mutation event or combination of events as defined in any one of claims 1 to or claims 13 to 17, or use of a DNA molecule which is the complement of a nucleic acid molecule as claimed in any one of claims 6 to 12 and which encodes an RNA
molecule that hybridizes with the mRNA encoded by a nucleic acid molecule as claimed in any one of claims 6 to 12, in combination with the use of the wild-type ion channel subunit, in the manufacture of a medicament for the treatment of epilepsy.
45. A method of treating a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness, comprising administering an antibody, as claimed in either one of claims 29 or 30, administration of an agonist, antagonist or modulator of an ion channel when it has undergone a mutation event or combination of events as defined in any one of claims 1 to 10 or claims 13 to 17, or administration of a DNA molecule which a.s the complement of a nucleic acid molecule as claimed in any one of claims 6 to 12 and which encodes an RNA molecule that hybridizes with the mRNA encoded by a nucleic acid molecule as claimed in any one of claims 6 to 12, in combination with administration of the wild-type ion channel subunit, to a subject an need of such treatment.
46. The use of an antibody, as claimed in claims 29 or 30, use of an agonist, antagonist or modulator of an ion channel when it has undergone a mutation event or combination of events as defined in any one of claims 1 to or claims 13 to 17, or use of a DNA molecule which is the complement of a nucleic acid molecule as claimed in any one of claims 6 to 12 and which encodes an RNA
molecule that hybridizes with the mRNA encoded by a nucleic acid molecule as claimed in any one of claims 6 to 12, in combination with the use of the wild-type ion channel subunit, in the manufacture of a medicament for the treatment of a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness.
47. Use of a nucleic acid molecule as claimed in any one of claims 6 to 12 for the screening of candidate pharmaceutical agents.
48. Use of a nucleic acid molecule as claimed in any one of claims 6 to 12 for the screening of candidate pharmaceutical agents useful for the treatment of epilepsy.
49. Use of a nucleic acid molecule as claimed in any one of claims 6 to 12 for the screening of candidate pharmaceutical agents useful for the treatment of a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness.
50. Use of a polypeptide as claimed in any one of claims 13 to 19 or claim 28, or a polypeptide complex as claimed in claim 20 for the screening of candidate pharmaceutical agents.
51. Use of a polypeptide as claimed in any one of claims 13 to 19 or claim 28, or a polypeptide complex as claimed in claim 20 for the screening of candidate pharmaceutical agents useful for the treatment of epilepsy.
52. Use of a polypeptide as claimed in any one of claims 13 to 19 or claim 28, or a polypeptide complex as claimed in claim 20 for the screening of candidate pharmaceutical agents useful for the treatment of a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness.
53. Use of a cell as claimed in any one of claims 22 to 26 for the screening of candidate pharmaceutical agents.
54. Use of a cell as claimed in any one of claims 22 to 26 for the screening of candidate pharmaceutical agents useful for the treatment of epilepsy.
55. Use of a cell as claimed in any one of claims 22 to 26 for the screening of candidate pharmaceutical agents useful for the treatment of a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness.
56. A compound when identified through a use as claimed in any one of claims 47 to 56.
57. A pharmaceutical composition comprising a compound as claimed in claim 56 and a pharmaceutically acceptable carrier.
58. A genetically modified non-human animal transformed with an isolated nucleic acid molecule as defined in any one of claims 6 to 12.
59. A genetically modified, non-human animal which has been transformed with two or more isolated nucleic acid molecules as claimed in any one of claims 6 to 12.
60. A genetically modified non-human animal as claimed in either one of claims 58 or 59 in which the animal is selected from the group consisting of rats, mice, hamsters, guinea pigs, rabbits, dogs, cats, goats, sheep, pigs and non-human primates such as monkeys and chimpanzees.
61. A method of producing a non-human transgenic animal containing a combination of two or more ion channel mutations, comprising the steps of:
(1) creating a non-human transgenic animal comprising a first nucleic acid molecule as claimed in any one of claims 6 to 12;
(2) creating one or more additional non-human, transgenic animals comprising a second nucleic acid molecule as claimed in any one of claims 6 to 12; and (3) conducting mating combinations so as to produce progeny containing combinations of two or more ion channel mutations which effectively mimic combinations of ion channel mutations responsible for human disease.
62. A non-human, transgenic animal produced by the process of claim 61.
63. The use of a genetically modified non-human animal as claimed in any one of claims 58 to 60 or a non-human transgenic animal as claimed in claim 62 in the screening of candidate pharmaceutical compounds.
64. The use of a genetically modified non-human animal as claimed in any one of claims 58 to 60 or a non-human transgenic animal as claimed in claim 62 in the screening of candidate pharmaceutical compounds useful in the treatment of epilepsy.
65. The use of a genetically modified non-human animal as claimed in any one of claims 58 to 60 or a non-human transgenic animal as claimed in claim 62 in the screening of candidate pharmaceutical compounds useful in the treatment of a disorder associated With ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness.
66. The use of an isolated nucleic acid molecule as claimed in any one of claims 6 to 12 for the diagnosis of epilepsy.
67. The use of an isolated nucleic acid molecule as claimed in any one of claims 6 to 12 for the diagnosis of a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness.
68. The use of a polypeptide as defined in any one of claims 13 to 17 or claim 28, or polypeptide complex as claimed in claim 20 in the diagnosis of epilepsy.
69. The use of a polypeptide as defined in any one of claims 13 to 17 or claim 28, or polypeptide complex as claimed in claim 20 in the diagnosis of a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness.
70. The use of an antibody as claimed in either one of claims 29 or 30 in the diagnosis of epilepsy.
71. The use of an antibody as claimed in either one of claims 29 or 30 ,in the diagnosis of a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness.
71. A method for the diagnosis of epilepsy comprising the steps of:
(1) obtaining DNA from a subject; and (2) comparing the DNA of one or more subunits of ion channels from said subject to the DNA of the corresponding native subunits;
wherein identification of one or more DNA molecules as claimed in any one of claims 6 to 12 is an indication of epilepsy, or a predisposition thereto.
72. A method for the diagnosis of a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness, comprising the steps of:
(1) obtaining DNA from a subject; and (2) comparing the DNA of one or more subunits of ion channels from said subject to the DNA of the corresponding native subunits;
wherein identification of one or more DNA molecules as claimed in any one of claims 6 to 12 a.s an indication of the disorder, or a predisposition thereto.
73. A method as claimed in either one of claims 71 or 72 wherein each DNA fragment is sequenced and the sequences compared.
74. A method as claimed in either one of claims 71 or 72 wherein the DNA fragments are subjected to restriction enzyme analysis.
75. A method as claimed in either one of claims 71 or 72 wherein the DNA fragments are subjected to SSCP analysis.
76. An isolated nucleic acid molecule encoding a mutant subunit of a mammalian nicotinic acetylcholine receptor (nAChR), wherein a mutation event selected from the group consisting of point mutations, deletions, insertions and rearrangements has occurred in the nucleotides outside of the M2 domain of the subunit of said mammalian nicotinic acetylcholine receptor, so as to produce an epilepsy phenotype.
77. An isolated nucleic acid molecule encoding a mutant subunit of a mammalian nicotinic acetylcholine receptor (nAChR), wherein a mutation event selected from the group consisting of point mutations, deletions, insertions and rearrangements has occurred in the nucleotides outside of the M2 domain of the subunit of said mammalian nicotinic acetylcholine receptor, so as to produce a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness.
78. An isolated nucleic acid as claimed in either one of claims 76 or 77 wherein said mutant subunit is the CHRNA4 subunit.
79. An isolated nucleic acid as claimed in claim 78 wherein said mutation event takes place in exon 5.
80. An isolated nucleic acid as claimed in claim 79 wherein said mutation event is selected from the group consisting of a C to T nucleotide substitution at position 1006, a G to A nucleotide substitution at position 1106 and a C to G nucleotide substitution at position 1421.
81. An isolated nucleic acid as claimed in either one of claims 76 or 77 wherein said mutant subunit is the CHRNB2 subunit.
82. An isolated nucleic acid as claimed in claim 81 wherein said mutation event takes place in exon 2 or exon 5.
83. An isolated nucleic acid as claimed in claim 82 wherein said mutation event is selected from the group consisting of a C to T nucleotide substitution at position 77, a C to G nucleotide substitution at position 901, a T
to C nucleotide substitution at position 923 and a G to A
nucleotide substitution at position 1235.
84. An isolated polypeptide, said polypeptide being a mutant subunit of a mammalian nicotinic acetylcholine receptor (nAChR), wherein a mutation event selected from the group consisting of substitutions, deletions, insertions and rearrangements has occurred outside of the M2 domain, so as to produce an epilepsy phenotype.
85. An isolated polypeptide, said polypeptide being a mutant subunit of a mammalian nicotinic acetylcholine receptor (nAChR), wherein a mutation event selected from the group consisting of substitutions, deletions, insertions and rearrangements has occurred outside of the M2 domain, so as to produce a disorder associated with ion channel dysfunction, including but not restricted to, hyper- or hypo-kalemic periodic paralysis, myotonias, malignant hyperthermia, myasthenia, cardiac arrhythmias, episodic ataxia, migraine, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia, anxiety, depression, phobic obsessive symptoms, neuropathic pain, inflammatory pain, chronic/acute pain, Bartter's syndrome, polycystic kidney disease, Dent's disease, hyperinsulinemic hypoglycemia of infancy, cystic fibrosis, congenital stationary night blindness or total colour-blindness.
86. An isolated polypeptide as claimed in either one of claims 84 or 85 wherein said mutant subunit is the CHRNA4 subunit.
87. An isolated polypeptide as claimed in claim 86 wherein said mutation event takes place in the intracellular loop of the CHRNA4 subunit.
88. An isolated polypeptide as claimed in claim 86 wherein said mutation event is selected from the group consisting of an R336C mutation, R369Q mutation and P474R
mutation.
89. An isolated polypeptide as claimed in either one of claims 84 or 85 wherein said mutant subunit is the CHRNB2 subunit.
90. An isolated polypeptide as claimed in claim 89 wherein said mutation event takes place in the signal sequence.
91. An isolated polypeptide as claimed ,in claim 90 wherein said mutation event is a T26M substitution.
92. An isolated polypeptide as claimed in claim 89 wherein said mutation event takes place in the M3 domain.
93. An isolated polypeptide as claimed in claim 92 wherein said mutation event is an L301V substitution or a v308A substitution.
94. An isolated polypeptide as claimed in claim 89 wherein said mutation event takes place in the intracellular loop of CHRNB2.
95. An isolated polypeptide as claimed a.n claim 94 wherein said mutation event is a G412D substitution.
CA2454073A 2001-07-18 2002-07-08 Mutations in ion channels Expired - Lifetime CA2454073C (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
AUPR6452 2001-07-18
AUPR6452A AUPR645201A0 (en) 2001-07-18 2001-07-18 Mutations in ion channels
AUPS0910 2002-03-05
AUPS0910A AUPS091002A0 (en) 2002-03-05 2002-03-05 Mutations in ion channels
AUPS2292 2002-05-13
AUPS2292A AUPS229202A0 (en) 2002-05-13 2002-05-13 Novel mutations
PCT/AU2002/000910 WO2003008574A1 (en) 2001-07-18 2002-07-08 Mutations in ion channels

Publications (2)

Publication Number Publication Date
CA2454073A1 true CA2454073A1 (en) 2003-01-30
CA2454073C CA2454073C (en) 2012-08-28

Family

ID=27158306

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2454073A Expired - Lifetime CA2454073C (en) 2001-07-18 2002-07-08 Mutations in ion channels

Country Status (9)

Country Link
US (2) US20050074764A1 (en)
EP (2) EP1407013B1 (en)
JP (1) JP2005501536A (en)
AT (1) ATE373089T1 (en)
AU (1) AU2002318972B8 (en)
CA (1) CA2454073C (en)
DE (1) DE60222422D1 (en)
NZ (2) NZ530258A (en)
WO (1) WO2003008574A1 (en)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005501536A (en) * 2001-07-18 2005-01-20 バイオノミックス リミテッド Mutations in ion channels
US7709225B2 (en) * 2001-07-18 2010-05-04 Bionomics Limited Nucleic acids encoding mutations in sodium channels related to epilepsy
AU2003904154A0 (en) 2003-08-07 2003-08-21 Bionomics Limited Mutations in ion channels
AU2003254168A1 (en) 2002-07-30 2004-02-16 Wyeth Parenteral formulations containing a rapamycin hydroxyester
AU2003901425A0 (en) * 2003-03-27 2003-04-10 Bionomics Limited A diagnostic method for epilepsy
AU2004263548B2 (en) * 2003-08-07 2007-09-13 Bionomics Limited Mutations in ion channels
JP2007537712A (en) * 2003-10-13 2007-12-27 バイオノミックス リミテッド Diagnostic methods for neonatal epilepsy syndrome or infantile epilepsy syndrome
AU2005318278A1 (en) * 2004-12-24 2006-06-29 Ares Trading S.A. Compositions and methods for treating mental disorders
JP2008546376A (en) * 2005-06-16 2008-12-25 バイオノミックス リミテッド Methods for diagnosing and treating epilepsy by detecting mutations in the SCN1A gene
KR20100122491A (en) * 2008-02-01 2010-11-22 크로모셀 코포레이션 Cell lines and methods for making and using them
EP2770325A1 (en) 2013-02-26 2014-08-27 Institut du Cerveau et de la Moelle Epiniere-ICM Mutations of DEPDC5 for diagnosing epilepsic diseases, disorders or conditions
CN116059349A (en) 2018-01-26 2023-05-05 国立大学法人东海国立大学机构 Therapeutic drug with target as receptor protein, detection drug, antibody combined with receptor protein and screening method of molecular targeting drug

Family Cites Families (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4016043A (en) 1975-09-04 1977-04-05 Akzona Incorporated Enzymatic immunological method for the determination of antigens and antibodies
US4172124A (en) 1978-04-28 1979-10-23 The Wistar Institute Method of producing tumor antibodies
US4474893A (en) 1981-07-01 1984-10-02 The University of Texas System Cancer Center Recombinant monoclonal antibodies
NZ207394A (en) 1983-03-08 1987-03-06 Commw Serum Lab Commission Detecting or determining sequence of amino acids
US4971903A (en) 1988-03-25 1990-11-20 Edward Hyman Pyrophosphate-based method and apparatus for sequencing nucleic acids
US5331573A (en) 1990-12-14 1994-07-19 Balaji Vitukudi N Method of design of compounds that mimic conformational features of selected peptides
NO175199C (en) 1991-12-05 1994-09-14 Kvaerner Fjellstrand As Flerskrogfartöy
AU701228B2 (en) * 1995-06-28 1999-01-21 University Of Bonn Diagnostic and treatment methods relating to Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE)
US5646040A (en) 1995-06-30 1997-07-08 Millennium Pharmaceutical, Inc. Mammalian tub gene
US6331614B1 (en) 1998-12-23 2001-12-18 Myriad Genetics, Inc. Human CDC14A gene
CA2394229C (en) * 1999-11-26 2010-04-13 Mcgill University Loci for idiopathic generalized epilepsy, mutations thereof and method using same to assess, diagnose, prognose or treat epilepsy
US6703439B2 (en) * 2000-02-09 2004-03-09 Mitsui Chemicals, Inc. Polyolefin resin composition and polyolefin film prepared from the same
AUPQ749100A0 (en) 2000-05-12 2000-06-08 Bionomics Limited New epilespy gene
US7157569B2 (en) 2000-06-20 2007-01-02 Bionomics Limited Mutation associated with epilepsy
AUPQ882600A0 (en) 2000-07-18 2000-08-10 Bionomics Limited Mutations in ion channels
US6661614B2 (en) * 2000-09-27 2003-12-09 Seagate Technology Llc Magnetless actuator for disc drive
AUPR220300A0 (en) * 2000-12-20 2001-01-25 Bionomics Limited New epilepsy gene
AUPR492201A0 (en) 2001-05-10 2001-06-07 Bionomics Limited Novel mutation
US7709225B2 (en) 2001-07-18 2010-05-04 Bionomics Limited Nucleic acids encoding mutations in sodium channels related to epilepsy
JP2005501536A (en) 2001-07-18 2005-01-20 バイオノミックス リミテッド Mutations in ion channels
AU2003904154A0 (en) 2003-08-07 2003-08-21 Bionomics Limited Mutations in ion channels
US7282336B2 (en) * 2001-07-18 2007-10-16 Bionomics Limited Method of diagnosing epilepsy
US20030157525A1 (en) 2001-11-26 2003-08-21 Mintier Gabriel A. Novel human G-protein coupled receptor, HGPRBMY31, and variants and methods of use thereof
AU2003901425A0 (en) 2003-03-27 2003-04-10 Bionomics Limited A diagnostic method for epilepsy
JP2008546376A (en) 2005-06-16 2008-12-25 バイオノミックス リミテッド Methods for diagnosing and treating epilepsy by detecting mutations in the SCN1A gene

Also Published As

Publication number Publication date
AU2002318972B2 (en) 2007-03-08
CA2454073C (en) 2012-08-28
EP1852505B1 (en) 2010-03-31
US7989182B2 (en) 2011-08-02
US20100136623A1 (en) 2010-06-03
JP2005501536A (en) 2005-01-20
DE60222422D1 (en) 2007-10-25
EP1852505A1 (en) 2007-11-07
AU2002318972A1 (en) 2003-03-03
ATE373089T1 (en) 2007-09-15
EP1407013B1 (en) 2007-09-12
EP1407013A4 (en) 2005-06-22
AU2002318972B8 (en) 2007-08-09
EP1407013A1 (en) 2004-04-14
US20050074764A1 (en) 2005-04-07
NZ530258A (en) 2006-01-27
WO2003008574A1 (en) 2003-01-30
NZ542048A (en) 2008-04-30

Similar Documents

Publication Publication Date Title
US7115393B2 (en) Melanocortin-1 receptor and methods of use
CA2454073A1 (en) Mutations in ion channels
JPH08507441A (en) Human neuronal nicotinic acetylcholine receptor compositions and methods for their use
CA2162648A1 (en) Excitatory amino acid receptor protein and related nucleic acid compounds
US7078515B2 (en) Sodium-channel alpha1-subunit and their polypeptides and their treatment of generalized epilepsy with febrile seizures plus
EP1292676B1 (en) Mutation associated with epilepsy
JP2007501601A5 (en)
JP2004500126A5 (en)
US7709225B2 (en) Nucleic acids encoding mutations in sodium channels related to epilepsy
US20050055733A1 (en) Small intestine and colon genes
US20060241015A1 (en) Cancer genes
NZ522372A (en) Mutation in the beta 2 nicotinic acetylcholine receptor subunit associated with nocturnal frontal lobe epilepsy
JP2004535178A5 (en)
WO1999049735A1 (en) Mpr-related abc transporter encoding nucleic acids and methods of use thereof
EP1092017B1 (en) Novel gaba-b receptor
US6635481B1 (en) Tbx3 gene and methods of using it
US20030078199A1 (en) Human EphA6 gene and polypeptide
JPH06319550A (en) Kainate-binding human cns receptor in eaa3 family
JP2002511263A (en) Vertebrate PATCHED-2 protein
US7053193B2 (en) Breast cancer transcription factor gene and uses
US6780595B2 (en) Human Tbx20 gene and uses
US7312026B2 (en) MRP-related ABC transporter encoding nucleic acids and methods of use thereof
US20030082548A1 (en) Brain selective transmembrane receptor gene
AU2002216826B2 (en) Sodium-channel alpha1-subunit and their polypeptides and their treatment of generalised epilepsy with febrile seizures plus
US7198911B2 (en) Identification and cloning of a novel human gene, RET16, involved in the intracellular signaling cascade

Legal Events

Date Code Title Description
EEER Examination request
MKEX Expiry

Effective date: 20220708