Biomarkers for bisphosphonate-responsive bone disorders
AssigneeUCL Business PLC
InventorsJohn Chamberlain, Halina Fitz-Clarence, Mark Thomas
Life of this patent
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Abstract
This invention relates to the finding that the presence of polymorphisms in and around the farnesyl diphosphate synthase (FDPS) gene is predictive of the densitometric response of patients with bone disorders, such as osteoporosis, subsequent to commencing treatment with amino-bisphosphonates. Methods relating to the identification of individuals having bone disorders which are responsive to bisphosphonates and predicting the responsiveness of individuals with bone disorders to treatment with a bisphosphonate are provided.
Claims30
A method of identifying an individual having a bone disorder which is responsive to bisphosphonate, or predicting the responsiveness of an individual with a bone disorder to treatment with a bisphosphonate, the method comprising:
- determining in a nucleic acid sample obtained from the individual, the presence or absence of a variant allele at one or more sites of polymorphism in the genomic region of the farnesyl diphosphate synthase (FDPS) gene,
- the presence of a variant allele at the one or more sites being indicative that the individual is responsive to bisphosphonates.
18-24. (canceled)
A method of treatment of a bone disorder in an individual having a variant allele at one or more sites of polymorphism in the genomic region of the farnesyl diphosphate synthase (FDPS) gene, the method comprising:
- administering a bisphosphonate to an individual in need thereof.
A method of identifying a cohort of individuals for use in testing candidate compounds for the treatment of bone disorders comprising
- identifying a population of individuals having a bone disorder,
- determining, in a genomic sample obtained from each of the individuals in said population, the presence or absence of a variant allele at one or more sites of polymorphism in the genomic region of the farnesyl diphosphate synthase (FDPS) gene, and,
- identifying a cohort of individuals within the population who have a variant allele at one or more sites of polymorphism in the genomic region of the farnesyl diphosphate synthase (FDPS) gene.
A method of identifying a compound useful in the treatment of a bone disorder comprising
- treating a population of individuals having a bone disorder with a candidate compound,
- determining in a genomic sample obtained from each of the individuals in said population, the presence or absence of a variant allele at one or more sites of polymorphism in the genomic region of the farnesyl diphosphate synthase (FDPS) gene
- identifying a cohort of individuals within the population who have a variant allele at one or more sites of polymorphism in the genomic region of the farnesyl diphosphate synthase (FDPS) gene,
- determining the responsiveness of the individuals in said cohort to the candidate compound.
A method of identifying an allelic variant which is associated with the responsiveness of a bone disorder to bisphosphonate comprising;
- providing a population of patients having a bone disorder and undergoing treatment with bisphosphonate,
- identifying a first cohort of patients in said population who are responsive to bisphosphonate and a second cohort who are unresponsive to bisphosphonate,
- determining the presence of allelic variants in the genomic region of the farnesyl diphosphate synthase (FDPS) gene in said first and second cohorts,
- wherein allelic variants present or occurring predominantly in the first but not the second cohort are candidate variants for association with response to bisphosphonate.
A kit for identifying an individual having a bone disorder which is responsive to bisphosphonate comprising:
- reagents for determining the presence or absence of a variant allele at one or more sites of polymorphism in the genomic region of the farnesyl diphosphate synthase (FDPS) gene in a genomic sample obtained from the individual,
- wherein the presence of a variant allele at the one or more sites being indicative that the individual is responsive to bisphosphonate treatment.
Dependencies are inferred from the claim text.