Method for predicting the onset of extrapyramidal symptoms (EPS) induced by an antipsychotic-based treatment
Inventors
Mas Herrero, Sergi • Gassó Astorga, Patricia • Malagelada Grau, Cristina • Bernardo Arroyo, Miquel • Lafuente Flo, Amalia
Assignees
Universitat de Barcelona UB • Hospital Clinic de Barcelona • Centro de Investigacion Biomedica en Red CIBER • Institut d'Investigacions Biomèdiques August Pi i Sunyer
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Publication Number
US-10954563-B2
Publication Date
2021-03-23
Expiration Date
Abstract
The invention relates to methods for predicting the onset of extrapyramidal symptoms (EPS) induced by an antipsychotic-based treatment as well as methods for providing personalized medicine to patients based on the sequence of several SNPs associated with the onset of EPS. The invention relates as well to kits for carrying out the diagnostic and predictive medicine methods.
Core Innovation
The invention relates to predicting and differentiating between a high risk and a low risk of a human subject developing extrapyramidal symptoms (EPS) induced by an antipsychotic-based treatment. The method determines, using a genotyping assay performed on genetic material isolated from the human subject, whether the subject has an allelic combination with respect to rs1130214, rs456998, rs7211818, and rs1053639. The resulting allelic combination is mapped to Haplotypes A-S or Haplotypes 1-27, where Haplotypes A-S are indicative of high risk of EPS and Haplotypes 1-27 are indicative of low risk of EPS.
After differentiation of risk status, the method treats the human subject with a suitable antipsychotic treatment selected based on the genetic risk. The suitable antipsychotic therapy is a low dopaminergic receptor D2 (DRD2) blockade potency anti-psychotic therapy if the subject has one of Haplotypes A-S indicative of high risk of EPS. The suitable antipsychotic therapy is a medium or high DRD2 blockade potency anti-psychotic therapy if the subject has one of Haplotypes 1-27 indicative of low risk of EPS.
The approach includes specific definitions of Haplotypes A-S and Haplotypes 1-27 based on allele identities at rs1130214, rs456998, rs7211818, and rs1053639. The patent further describes that genotyping can be carried out using nucleic-acid detection assays and allele-determining assays, including oligonucleotides and probes associated with the gene products AKT1, FCHSD1, RPTOR, and DDIT4. Genetic test results are linked to treatment selection and optional supportive therapy based on EPS risk status.
Claims Coverage
The document includes one independent claim with a method that differentiates high-risk versus low-risk EPS using allelic combinations from four specified SNPs, and then selects a suitable antipsychotic based on DRD2 blockade potency.
Differentiating EPS risk using four SNP allelic combinations and haplotype mapping
Determining via a genotyping assay performed on genetic material isolated from the human subject whether the human subject has an allelic combination with respect to rs1130214, rs456998, rs7211818, and rs1053639 as set forth in Haplotypes A-S or as set forth in Haplotypes 1-27, wherein an allelic combination in Haplotypes A-S is indicative of a high risk of the human subject developing EPS and an allelic combination in Haplotypes 1-27 is indicative of a low risk of the human subject developing EPS.
Treating based on DRD2 blockade potency selected from EPS genetic risk status
Administering a suitable anti-psychotic therapy wherein the suitable anti-psychotic therapy is a low dopaminergic receptor D2 (DRD2) blockade potency anti-psychotic therapy if the human subject has one of Haplotypes A-S indicative of a high risk of the human subject developing EPS, and a medium or high DRD2 blockade potency anti-psychotic therapy if the human subject has one of Haplotypes 1-27 indicative of a low risk of the human subject developing EPS.
Overall, claim coverage is anchored by a two-part method: genotyping rs1130214, rs456998, rs7211818, and rs1053639 and mapping the allelic combination to Haplotypes A-S or Haplotypes 1-27, then administering an antipsychotic treatment selected according to whether low DRD2 blockade potency versus medium or high DRD2 blockade potency is indicated by the haplotype-defined risk status.
Stated Advantages
Documented Applications
No documented applications found
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