What pharmacogenetics research projects are we developing at the University Hospital of Burgos?
Polymorphisms in the oxytocin receptor and their association with apathy and impaired social cognition in Huntington's disease
Principal Investigator: Miriam Saiz Rodríguez and Esther Cubo Delgado. With the invaluable assistance of Dora Koller (Yale University School of Medicine).
Study on the role of the gene coding for the oxytocin receptor (OXTR) and its relationship to apathy and social cognition in Huntington's disease in 2230 patients and controls. The data used in this work were generously provided by participants in the Enroll-HD study and made available by CHDI Foundation, Inc. Enroll-HD is a global clinical research platform aimed at accelerating progress toward therapies for Huntington's disease; baseline data sets are collected annually from all research participants as part of this multicenter longitudinal observational study. Enroll-HD is sponsored by CHDI Foundation, Inc, a non-profit biomedical research organization dedicated exclusively to the development of therapies for Huntington's disease. Enroll-HD would not be possible without the vital contribution of research participants and their families. The data used in this work were generously provided by the combined efforts of the Genetic Modifiers of Huntington's Disease (GeM-HD) Consortium.
iPHARMGx Project: National collaborative study to evaluate the effectiveness and efficiency of the implementation of pharmacogenetic biomarkers through an early genotyping strategy in the NHS.
National Consortium led by Alberto Borobia (Hospital de La Paz, Madrid)
Principal Investigator: Miriam Saiz Rodríguez
This project proposes the selection and conduct of adaptive clinical trials in at-risk populations susceptible to receive statins, tacrolimus or anti-TNF that will be genotyped and randomized to one of two treatment arms: experimental (selection and/or dose adjustment based on genetic information) or control (standard clinical practice, in which no genetic information is obtained). Patients will be followed until the occurrence of the clinical event (efficacy and/or toxicity). The results obtained will be used to try to implement the relevant biomarkers in clinical practice.
Funded by: Instituto de Salud Carlos III, Convocatoria Proyectos de Medicina Personalizada 2022.
Search for biomarkers predictive of bortezomib toxicity in patients with multiple myeloma
Principal Investigator: Miriam Saiz Rodríguez
Research project that aims to identify predictive biomarkers of bortezomib toxicity in patients with multiple myeloma, paying special attention to peripheral neuropathy and thrombocytopenia. Project awarded in the second edition of the HNA Foundation Prize for Scientific Health Research, focused on the study of pharmacogenetic polymorphisms and their consequences on the side effects of chemotherapy and the treatment of these diseases.
Funded by: Fundación hna
Factors related to treatment effects in Huntington's disease: a multidisciplinary approach
Principal Investigator: Esther Cubo Delgado
This study aims to analyze the main factors (intrinsic factors, such as pharmacogenetics, and extrinsic factors, such as pre-metabolism of drugs by the intestinal microbiome, biological factors (sex, age) and comorbidities/drug interactions) associated with standard treatment of Huntington's disease in terms of efficacy and presence of adverse reactions.
FLUOROPYRIMIDINE-SCORE: design of a predictive score for fluoropyrimidine toxicity combining the measurement of plasma uracil levels with the determination of variants in genes of the pharmacokinetic-pharmacodynamic pathway of these drugs
Principal Investigator: Beatriz Llorente Ayala
Prospective, multidisciplinary study to design a predictive score for fluoropyrimidine toxicity by combining the measurement of plasma uracil levels with the determination of variants in genes of the pharmacokinetic and pharmacodynamic pathway of these drugs.
Randomized clinical trial to evaluate the utility of CYP2D6 genotyping to improve the efficacy and safety of tramadol in the treatment of acute postoperative pain.
Multicenter project led by Francisco Abad Santos
Principal Investigator: Miriam Saiz Rodríguez
Clinical trial to validate the use of the CYP2D6 biomarker to guide treatment of the analgesic tramadol. Patients will be genotyped and randomized to one of three treatment arms: experimental (selection and/or dose adjustment based on genetic information) or control (usual clinical practice, in which no genetic information is obtained, and a treatment choice between dexketoprofen and tramadol is assigned). Patients will be followed up for 7 days.
Funded by: Instituto de Salud Carlos III, convocatoria Investigación Clínica Independiente
Identification of transporter polymorphisms influencing pharmacokinetics and response to metformin in healthy volunteers and patients with type 2 diabetes mellitus.
Principal Investigator: Estefanía Santos Mazo
The objective of this study is to identify clinical and genetic factors that condition the pharmacokinetics and pharmacodynamics of metformin in healthy volunteers and the response to metformin in patients diagnosed with type 2 diabetes mellitus, with the aim of developing an algorithm to predict whether or not a patient will respond satisfactorily to metformin treatment, based on: genotyping of the polymorphisms described, clinical-demographic characteristics and baseline plasma levels of glycosylated hemoglobin.
Influence of ABCB1 polymorphisms on ibrutinib transport in vitro and its possible implication in the treatment of chronic lymphocytic leukemia.
Principal Investigator: Antonio Sanz Solas
The aim of this study is to demonstrate whether ibrutinib is a substrate, inhibitor or inducer of P-gp and to study the influence of the C3435T, C1236T and G2677T/A polymorphisms in the ABCB1 gene on the transport of ibrutinib. For this purpose, cellular models will be developed and their feasibility and usefulness in P-gp expression and function will be demonstrated. Subsequently, transport and expression assays will be performed in the presence of ibrutinib. If our hypothesis is confirmed, the basis will be laid for a subsequent in vivo study to confirm the relationship of these polymorphisms with a greater occurrence of adverse reactions and the confirmation that patients carrying mutated alleles have a higher risk of ibrutinib toxicity.
Therapeutic monitoring and pharmacogenetic study of ibrutinib in patients with chronic lymphocytic leukemia.
Principal Investigator: Jorge Labrador Gómez
Therapeutic drug monitoring (TPM) of ibrutinib will be performed in patients with chronic lymphocytic leukemia (CLL) to evaluate the influence of plasma levels and genetic polymorphisms on treatment efficacy and safety. The project will last one year and will include 30 patients, whose plasma concentrations will be measured by high-performance liquid chromatography coupled to mass spectrometry. The identification of factors influencing the efficacy and safety of ibrutinib will lay the foundation for precision medicine and help reduce the rate of adverse drug reactions and associated costs.
Identification of clinical and pharmacogenetic predictors of response to new oral anticoagulants in the treatment of nonvalvular atrial fibrillation.
Multicenter project led by Francisco Abad Santos
Principal Investigator: Miriam Saiz Rodríguez
The aim of this study is to identify the clinical and genetic factors that condition the response to the new oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) (NOAC) in patients with nonvalvular atrial fibrillation (NVAF) in daily clinical practice. The main objective is to study the impact of polymorphisms in the genes involved in the pharmacokinetics and pharmacodynamics of these drugs on clinical events (bleeding, stroke and cardiovascular mortality), as well as on plasma concentrations and anticoagulant activity.
Funded by: Instituto de Salud Carlos III, convocatoria Proyectos de I+D+I en Salud
