Identification of two principal mutations in ion channels associated with idiopathic generalised epilepsies
OwnerSamuel Frank Berkovicinventor
Life of this patent
Estimating the term…
Abstract
A method for identifying the molecular defects responsible for the idiopathic generalised epilepsies (IGE), comprising the steps of: 1) providing sequence information for ion channel subunits; 2) screening a nucleic acid or peptide isolated from a patient affected by an IGE for molecular defects in the ion channel subunits in order to identify two principal defects associated with the IGE; and 3) correlating the two principal molecular defects identified with clinical observations in order to establish the combination of mutant subunits involved in the IGE.
Claims31
A method for identifying the molecular defects responsible for the idiopathic generalised epilepsies (IGE), comprising the steps of:
- 1) providing sequence information for ion channel subunits;
- 2) screening a nucleic acid or peptide isolated from a patient affected by an IGE for molecular defects in the ion channel subunits in order to identify two principal defects associated with the IGE;
- and
- 3) correlating the two principal molecular defects identified with clinical observations in order to establish the combination of mutant subunits involved in the IGE.
A method for establishing the loci of molecular defects of ion channel subunit genes responsible for the idiopathic generalised epilepsies (IGE), comprising the steps of:
- 1) obtaining a DNA sample from a patient affected with epilepsy;
- 2) comparing the DNA sample with that from a corresponding wild type DNA sample;
- 3) identifying those patient DNA samples in which two loci segregate with the disease;
- and
- 4) determining the location of the two abnormal loci.
A method of diagnosis of an IGE, comprising the steps of:
- 1) providing a DNA sample from a patient suspected of an IGE;
- 2) screening the sample for molecular defects in the genes encoding ion channel subunits;
- 3) establishing the presence or absence of mutations associated with IGE and, where such mutations are present, identifying the two principal mutations associated with the IGE;
- 4) comparing the identified molecular defects to pre-existing data correlating molecular defects to sub-syndromes of IGE;
- and
- 5) identifying the IGE.
A method of diagnosis of an IGE, comprising the steps of:
- 1) providing a protein sample from a patient suspected of an IGE;
- 2) screening the sample for molecular defects in ion channel subunits;
- 3) establishing the presence or absence of molecular defects and, where molecular defects are present, identifying two principal molecular defects associated with the IGE;
- 4) comparing the identified molecular defects with pre-existing data correlating molecular defects with sub-syndromes of IGE;
- and
- 5) identifying the IGE.
An expression vector transformed with either a DNA molecule which encodes two mutant ion channel subunits, each containing a molecular defect or with two DNA molecules, each encoding an ion channel subunit with a molecular defect, in order that an animal in which the vector expresses protein has an IGE phenotype.
A genetically modified, non-human animal in which two ion channel subunits, each containing a molecular defect, are expressed in order that the animal has an IGE phenotype.
A method of producing a non-human transgenic animal containing a combination of two ion channel mutations comprising the steps of:
- 1) creating a non-human transgenic animal containing a mutation in a single ion channel subunit;
- 2) creating a second, non-human, transgenic animal containing a mutation in a different ion channel subunit;
- and
- 3) conducting mating combinations so as to produce progeny containing combinations of two ion channel mutations which effectively mimic combinations of ion channel mutations responsible for human IGE cases.
A method for the treatment of an IGE, comprising administering to a patient with two principal molecular defects in their ion channel subunits which are causative of the IGE, one or more therapeutic agents which, singly or collectively, overcome or ameliorate the effect of the two principal molecular defects.
Use of a wild-type ion channel subunit polypeptide, a nucleic acid encoding a wild-type ion channel subunit, a nucleic acid encoding the complement of an ion channel subunit gene, or an agonist, modulator or antagonist of an ion channel subunit containing one of two principal molecular defects causative of an IGE, in the preparation of a medicament for the treatment of the IGE.
A method of screening for therapeutic agents useful in the treatment of an IGE, wherein two principal molecular defects in the ion channel subunits of a subject are causative of the IGE, comprising introducing a potential therapeutic agent to a model system in which interaction with the two principal molecular defects is possible, and establishing which therapeutic agents overcome or ameliorate the effect of the two principal defects.
Dependencies are inferred from the claim text.