33 results about "Pharmacogenetics" patented technology

The present invention provides methods of designing PCR primers that allow the efficient and simultaneous amplification of a large number of different desired DNA fragments in a single multiplex PCR and minimize the formation of nonspecific extensions of undesired DNA fragments. The present invention allows a multiplex PCR to use at least 50 pairs of primers and produce at least 50 DNA fragments of interest. The present invention significantly broadens the application of multiplex PCR in the identification of multiple genes related to multifactorial diseases, the genome-scale detection of genetic alterations, the studies in large-scale pharmacogenetic reactions, the genotyping genetic polymorphism in a large population, the gene expression profiling in various samples, and high throughput genotyping technologies.

The present invention relates to methods for detecting polymorphisms in enzymes related to drug metabolizm (Drug Metabolizing Enzymes or DMEs) such as uridine diphosphate glucuronosyl transferase (UGT) gene promoter, cytochrome p450, with a non-amplified oligonucleotide detection assays. The present invention also relates to pharmacogenetic DME detection assay kits.

The present invention provides a method for the determining the appropriate therapy and/or prognosis for a patient diagnosed with a non-Alzheimer's disease (AD) neurological disease based upon the patient's apoE allele load. The invention also provides a method for the identification of human subjects with a non-AD neurological disease that are likely to respond in clinical trials that test pharmaceuticals useful in the treatment of neurological diseases.

The present invention provides methods for diagnosing a neurological disease and/or for determining the predisposition of a subject to a neurological disease and/or for determining a subject at risk of developing a neurological disease, the method comprising detecting a marker in a glycogen synthase kinase 3β gene or expression product thereof and a microtubule-associated protein tau (MAPT) gene or expression product thereof. The present invention also provides pharmacogenetic methods, e.g., for identifying a subject that will respond to treatment with a therapeutic compound.

The present invention is directed to methods and compositions for determining the presence or absence of polymorphisms within an ABCC2, UGT1A1, and/or SLCO1B1 gene and correlating these polymorphisms with activity levels of their gene products and making evaluations regarding the effect on their substrates, particularly those substrates that are drugs. In addition, there are methods and compositions of evaluating the risk of an individual for developing toxicity or adverse event(s) to an ABCC2, UGT1A1, and/or SLCO1B1 substrate. In some embodiments, the invention concerns methods and compositions for determining the presence or absence of ABCC2 3972C>T variant and predicting or anticipating the level of activity of ABCC2 and determining dosages of an ABCC2 drug substrate, such as irinotecan, in a patient. Such methods and compositions can be used to evaluate whether irinotecan-based therapy, or therapy involving other ABCC2 substrates, may pose toxicity problems if given to a particular patient or predicting their efficacy. Alterations in suggested therapy may ensue based on genotyping results.

The present invention relates to a web-based computer-aided method and a system for providing personalized recommendations about drug use, based on pharmacogenetic information regarding genes and genetic variants associated to metabolism and genes and genetic variants which are not associated to metabolism, and which comprises automatically generating and displaying, by means of a graphical user interface (GUI) of a dynamic webpage, the personalized recommendations highlighting the ones associated to the highest adverse drug reactions.

The present invention also relates to a computer-readable medium which contains program instructions for a computer to perform the method for providing personalized recommendations about drug use of the invention.

The present invention also relates to a web-based computer-aided method and a system for generating a dynamic webpage, and a further computer-readable medium which contains program instructions for a computer to perform the method for generating a dynamic webpage.

The present invention is directed to methods and compositions for determining the presence or absence of polymorphisms within an ABCC2, UGT1A1, and/or SLCO1B1 gene and correlating these polymorphisms with activity levels of their gene products and making evaluations regarding the effect on their substrates, particularly those substrates that are drugs. In addition, there are methods and compositions of evaluating the risk of an individual for developing toxicity or adverse event(s) to an ABCC2, UGT1A1, and/or SLCO1B1 substrate. In some embodiments, the invention concerns methods and compositions for determining the presence or absence of ABCC2 3972C>T variant and predicting or anticipating the level of activity of ABCC2 and determining dosages of an ABCC2 drug substrate, such as irinotecan, in a patient. Such methods and compositions can be used to evaluate whether irinotecan-based therapy, or therapy involving other ABCC2 substrates, may pose toxicity problems if given to a particular patient or predicting their efficacy. Alterations in suggested therapy may ensue based on genotyping results.

Cell lines harboring a range of polymorphisms using recombinant cytochrome P450 or other chemical-metabolizing enzymes in a parent cell line that is minimally expressing or devoid of its own cytochrome P450 protein or other chemical-metabolizing enzymes of interest can be placed into an array format to enable high throughput screening of one or more chemicals for CYP450 or other enzyme-dependent metabolism (FIG. 9). Processing of the cells can be automated, done en-masse through use of an array having a substrate upon which a plurality of cell lines with exogenous chemical-metabolizing enzymes are coupled, and both relative and quantitative metabolism rates determined using mass spectrometry over time. Thus, methods are disclosed to measure, for example, the effects of cytochrome P450 polymorphisms on clinical drug metabolism in a high throughput manner for drug development and genetically personalized diagnostics and treatment regimens.

Polymorphisms in the beta-1 adrenergic receptor that (1) affect tolerability to beta-blocker treatment or (2) influence responsiveness to beta-blocker treatment are disclosed. Additionally, methods of predicting that an individual would obtain clinical improvement in left ventricular function as a result of β-blocker therapy or identifying at least one individual that would obtain a clinical improvement in left ventricular function as a result of β-blocker therapy are provided. Methods of treating patients characterized by such polymorphisms are also illustrated.

The invention discloses a detecting kit for polymorphism of warfarin pharmacogenetics genes CYP2C9 and VKORC1, belongs to the technical field of genetic test diagnosis, and is used for auxiliary determination of warfarin dosage of a patient. The kit disclosed by the invention comprises specific primers and specific probes which are used for detecting mutations at the sites rs1057910 and rs9923231; the specific primers comprise upstream primers and downstream primers; the specific probes comprise a positive probe and a negative probe; the specific primers and the specific probes of the rs1057910 are respectively the upstream primers as shown in SEQ ID NO.1 and SEQ ID NO.3, the downstream primers as shown in SEQ ID NO.2 and the SEQ ID NO.4, the positive specific fluorescent probe as shown in SEQ ID NO.5, and a negative specific fluorescent probe as shown in SEQ ID NO.6; and the detecting kit for the polymorphism of the warfarin pharmacogenetics genes CYP2C9 and VKORC1 can be used for individualized treatment of warfarin according to genetic genes, and has important significance in subsequent research.

Methods of and kits for determining the pharmacogenetic, pharmacokinetic and cellular basis of bisphosphonate-induced osteonecrosis of the jaw (BONJ) involve associating particular proteins and particular single nucleotide polymorphisms with a risk for developing BONJ after receiving bisphosphonate treatment. Methods and kits for identifying the genetic basis for a patient's predisposition to BONJ, and methods of identifying patients who are prone to develop BONJ following bisphosphonate administration provide for the development of a tool for physicians to prescribe treatment protocols for BONJ patients based on the patients' genomes (“personal/tailored medicine”). A haplotype tagging SNP approach was used to analyze candidate genes involved in bone absorption and destruction and to examine the influence of genetic variants on the susceptibility of BONJ. Bone biomarkers of BONJ were examined using molecular cell techniques. The methods described herein can be used to identify differences in how patients are genetically predisposed to BONJ as well as genetic differences amongst patients that account for differences in how these patients clear bisphosphonate s from their systems. Determining such genetic differences provides for improved monitoring of the drugs used to treat BONJ, improved prevention of BONJ, and optimized treatment for patients having BONJ or predisposed to BOND.

The invention provides a pharmaceutical composition for specifically regulating activity of hypothalamic ventral nucleus astrocytes and application of the pharmaceutical composition. The pharmaceutical composition comprises clozapine nitrogen oxide and a viral vector used for infecting the astrocytes; the viral vector comprises a pharmaceutical genetics regulatory element hM4Di or hM3Dq. The pharmaceutical composition can selectively activate a Gi pathway or a Gq pathway of astrocytes, and by means of the pharmaceutical composition. According to the invention, it is proved that anxiety-like behaviors and bone loss phenomena induced by chronic pressure stress can be intervened by selectively adjusting the activity of VMH astrocytes.

Provided are therapeutic virus vectors, particularly, recombinant adeno-associated virus (rAAV) vectors, designed to contain an enhancer sequence that specifically restricts expression of an effector gene (e.g., an SCN1A-encoding polynucleotide, Gq-DREADD-encoding polynucleotide, or PSAM-encoding polynucleotide) contained in the vector to PV-expressing GABAergic interneuron or to neuron cell populations in the brain. The rAAV vectors, compositions and methods thereof are useful for treating subjects afflicted with neuropathologies, seizures, pharmacologically-intractable forms of epilepsy including Dravet syndrome (DS), a form of infantile epilepsy associated with severe seizures, cognitive impairment and premature death, as the cause of DS involves loss of function of a sodium channel encoded by the SCN1A gene. The described vectors restore expression of effector genes to the appropriate interneuron or neuron cell populations with specificity and sensitivity, advantageously to address the root cause of the disease by restoring the excitation-inhibition balance by means of gene-therapy (with SCN1A) or pharmacogenetics.

The present invention relates to pharmacogenetics, more specifically to strategies involving biomarkers associated with the clinical response to a compound before or during treatment of a cartilage disorder, such as osteoarthritis. The present invention more particularly relates to the combination of JSW measurements and level of specific proteins present in the blood, serum, synovial fluid or in the urine, which can be used in strategies such as patients' enrichment in clinical trials, patients' selection strategy before or during treatment or for adapting the treatment of a patient in the frame of treatments for cartilage disorder, such as osteoarthritis.

We have identified panels of proxy single nucleotide polymorphisms (SNPs) that are highly predictive of particular HLA risk alleles, and concordant across multi-ethnic populations. Accordingly, methods are provided involving clinical DNA testing for HLA panel markers to assess risk for life-threatening adverse drug reactions associated with the human leucocyte antigen (HLA) alleles HLA-B*57:01, HLA-B*15:02, HLA-A*31:01 and HLA-B*58:01. Methods of treating a subject with a drug associated with an adverse drug reaction (ADR) are provided. Based on the assessed risk to a subject for developing an adverse drug reaction in response to a drug, appropriate administrations of the drug can be made. In some embodiments of the method, the drug is administered when there is a low assessed risk of ADR in the subject. Alternatively, when there is a high assessed risk of ADR in the subject, a reduced dosage of the drug, or no drug, can be administered.

Methods of and kits for determining the pharmacogenetic, pharmacokinetic and cellular basis of bisphosphonate-induced osteonecrosis of the jaw (BONJ) involve associating particular proteins and particular single nucleotide polymorphisms with a risk for developing BONJ after receiving bisphosphonate treatment. Methods and kits for identifying the genetic basis for a patient's predisposition to BONJ, and methods of identifying patients who are prone to develop BONJ following bisphosphonate administration provide for the development of a tool for physicians to prescribe treatment protocols for BONJ patients based on the patients' genomes (“personal/tailored medicine”).