MP12-Otology and Otoneurology
Precision Medicine / IBS-MP12 / Consolidated
Recurrent vertigo is a very common health problem caused by a disorder of the vestibular system. The most common causes are benign paroxysmal positional vertigo, vestibular migraine, and Ménière's disease. Among these, Ménière's disease is the most severe form of vertigo and disabling tinnitus. Ménière's disease (MD) is a chronic multifactorial disorder of the inner ear that causes progressive sensorineural hearing loss, episodes of recurrent vertigo, and tinnitus, with a prevalence of 75 cases per 100.000 inhabitants in Spain. Familial MD accounts for 8–9% of cases and presents genetic heterogeneity with autosomal dominant, recessive, and mitochondrial inheritance patterns.
Our group has assembled the largest collection of human DNA samples from MS patients, including more than 100 multicase families and more than 2000 sporadic cases, with the aim of identifying MS-associated genes. To this end, we performed genotyping in sporadic cases, identifying common variants in non-coding regions, and whole-exome sequencing in multicase families to identify very rare or de novo variants with high penetrance in coding regions.
The results have identified several loci on chromosome 6p21.33 in cases with involvement of both ears that could define autoimmune inner ear disease. Furthermore, we have defined novel mutations for familial MS in the genes FAM136A, PRKCB, DTNA, DPT, and SEMA3D in three families with autosomal dominant inheritance. We are currently developing a stem cell model of the disease to evaluate the functional role of these genes.
Research lines
- Line 1- Genomic architecture of sporadic Menière's disease.
- Line 2- Identification of genes associated with familial Menière's disease.
- Line 3- Molecular mechanisms in autoimmune / autoinflammatory disease of the inner ear.
- Line 4- Development of a cellular model of Menière's disease
- Line 5- Molecular bases of hyperacusis and tinnitus in Menière's disease.
- Line 6- Genetic bases of cerebellar ataxia, peripheral neuropathy and vestibular areflexia (CANVAS)
Research networks
- CIBERER - Rare Diseases Network Biomedical Research Center
Keywords
vertigo / tinnitus / Meniere disease / vestibular migraine / sequencing / autoimmunity / autoinflammation molecular diagnosis / mechanisms of disease / Meniere disease / vestibular disorders / genomics / exome sequencing / stem cells / autoimmune inner ear disease
Adela Serrano Herrera
Juan Martin-Lagos Martinez
FRANCISCA CARA LUPIAÑEZ
ALBERTO MANUEL PARRA PEREZ
Alberto Bernal Robledano
PATRICIA PEREZ CARPENA
JUAN MANUEL ESPINOSA SANCHEZ
JUAN GARCIA VALDECASAS
JOSE ANTONIO LOPEZ ESCAMEZ
MARTA MARTINEZ MARTINEZ
MARIA JESUS MARTINEZ MARTINEZ
MARIA MATA FERRON
MARIA DEL CARMEN MOLEÓN GONZALEZ
Unlocking the effective alliance of β-lapachone and hydroxytyrosol against triple-negative breast cancer cells
PHARMACOTHERAPY, 2024;
FI: 6,9; D1
Cognitive Screening and Hearing Assessment in Patients With Chronic Tinnitus
CLINICAL AND EXPERIMENTAL OTORHINOLARYNGOLOGY, 2024;
FI: 2,9; D1
A Systematic Review on Heritability of Sudden Sensorineural Hearing Loss
LARYNGOSCOPE, 2024;
FI: 2,2; Q1
Domingo Sánchez y Sánchez (1860-1947): Cajal's man on the nervous system of invertebrates
FRONTIERS IN NEUROANATOMY, 2024;
FI: 2,1; Q1
Epidemiology and genetics of Meniere's disease
CURRENT OPINION IN NEUROLOGY, 2024;
FI: 4,1; Q1
Immune-Related Disorders Associated With Meniere's Disease: A Systematic Review and Meta-analysis
OTOLARYNGOLOGY-HEAD AND NECK SURGERY, 2023;
FI: 3,4; Q1
The pediatric leukemia oncoprotein NUP98-KDM5A induces genomic instability that may facilitate malignant transformation
CELL DEATH & DISEASE, 2023;
FI: 9; Q1
Application of Human Stem Cells to Model Genetic Sensorineural Hearing Loss and Meniere Disease
CELLS, 2023;
FI: 6; Q2
Magnetic resonance imaging of endolymphatic hydrops: Controversies and common ground, comment on: A plea for systematic literature analysis and conclusive study design
JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION, 2023;
FI: 2,3; Q4
The vestibular system: Contributions of Lorente de No'
JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION, 2023;
FI: 2,3; Q4
A novel nonsense variant in the CENPP gene segregates in a Swiss family with autosomal dominant low-frequency sensorineural hearing loss
EUROPEAN JOURNAL OF HUMAN GENETICS, 2022;
FI: 5,351; Q1
A Predictive Model of Bilateral Sensorineural Hearing Loss in Meniere Disease Using Clinical Data
EAR AND HEARING, 2022;
FI: 3,562; Q1
Cytokines and Inflammation in Meniere's Disease
CLINICAL AND EXPERIMENTAL OTORHINOLARYNGOLOGY, 2022;
FI: 3,34; Q1
Defective alpha-tectorin may involve tectorial membrane in familial Meniere disease
CLINICAL AND TRANSLATIONAL MEDICINE, 2022;
FI: 8,554; Q1
Involvement of the PI3K/AKT Intracellular Signaling Pathway in the AntiCancer Activity of Hydroxytyrosol, a Polyphenol from Olea europaea, in Hematological Cells and Implication of HSP60 Levels in Its Anti-Inflammatory Activity
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022;
FI: 6,208; Q1
CSVS, a crowdsourcing database of the Spanish population genetic variability
NUCLEIC ACIDS RESEARCH, 2021;
FI: 16,971; D1
Burden of rare variants in synaptic genes in patients with severe tinnitus: An exome based extreme phenotype study
EBIOMEDICINE, 2021;
FI: 8,143; Q1
Clinical and Cytokine Profile in Patients with Early and Late Onset Meniere Disease
JOURNAL OF CLINICAL MEDICINE, 2021;
FI: 4,242; Q1
DNA Methylation Signature in Mononuclear Cells and Proinflammatory Cytokines May Define Molecular Subtypes in Sporadic Meniere Disease
BIOMEDICINE, 2021;
FI: 6,081; Q1
Do we need to reconsider the classification of vestibular migraine?
EXPERT REVIEW OF NEUROTHERAPEUTICS, 2021;
FI: 4,618; Q2
Burden of Rare Variants in the OTOG Gene in Familial Meniere's Disease
EAR AND HEARING, 2020;
FI: 3,129; D1
Association between Hyperacusis and Tinnitus
JOURNAL OF CLINICAL MEDICINE, 2020;
FI: 3,303; Q1
A Systematic Review on the Association of Acquired Human Cytomegalovirus Infection with Hearing Loss
JOURNAL OF CLINICAL MEDICINE, 2020;
FI: 3,303; Q1
A Systematic Review of Extreme Phenotype Strategies to Search for Rare Variants in Genetic Studies of Complex Disorders
GENES, 2020;
FI: 3,759; Q2
Clinical and molecular genetics of Meniere's disease
MEDIZINISCHE GENETIK, 2020;
FI: 0,964; Q4
Video Head-Impulse Testing vs. Clinical Diagnosis of Vestibular Disorders
JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY, 2019;
FI: 3,502; D1
Recommendations on Collecting and Storing Samples for Genetic Studies in Hearing and Tinnitus Research
EAR AND HEARING, 2019;
FI: 2,954; D1
Standardized profiling for tinnitus research: The European School for Interdisciplinary Tinnitus Research Screening Questionnaire (ESIT-SQ)
HEARING RESEARCH, 2019;
FI: 2,952; D1
Systematic review of magnetic resonance imaging for diagnosis of Meniere's disease
JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION, 2019;
FI: 2,774; Q1
Peripheral vestibular disorders: an update
CURRENT OPINION IN NEUROLOGY, 2019;
FI: 4,647; Q1
Genetic contribution to vestibular diseases
JOURNAL OF NEUROLOGY, 2018;
FI: 3,783; Q1
Proinflammatory cytokines and response to molds in mononuclear cells of patients with Meniere's disease
SCIENTIFIC REPORTS, 2018;
FI: 4,122; Q1
Genetics of vestibular syndromes
CURRENT OPINION IN NEUROLOGY, 2018;
FI: 4,01; Q1
Clinical and Functional Characterization of a Missense ELF2 Variant in a CANVAS Family
FRONTIERS IN GENETICS, 2018;
FI: 4,151; Q1
Innovations in Doctoral Training and Research on Tinnitus: The European School on Interdisciplinary Tinnitus Research (ESIT) Perspective
FRONTIERS IN AGING NEUROSCIENCE, 2018;
FI: 3,582; Q1
Genetic susceptibility to bilateral tinnitus in a Swedish twin cohort.
GENETICS IN MEDICINE, 2017;
FI: 8,229; D1
Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis
CLINICAL OTOLARYNGOLOGY, 2017;
FI: 2,523; Q1
Regulation of Fn14 Receptor and NF-kappa B Underlies Inflammation in Meniere's Disease
FRONTIERS IN IMMUNOLOGY, 2017;
FI: 6,429; Q1
High-frequency sensorineural hearing loss associated with vestibular episodic syndrome
CLINICAL OTOLARYNGOLOGY, 2017;
FI: 2,523; Q1
Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in autosomal dominant familial Meniere's disease
EUROPEAN JOURNAL OF HUMAN GENETICS, 2017;
FI: 4,287; Q1
A novel missense varint in PRKCB segregates low-frequency hearing loss in an autosomal dominant family with Meniere's disease
HUMAN MOLECULAR GENETICS, 2016;
FI: 5,985; D1
Clinical Subgroups in Bilateral Meniere's Disease
FRONTIERS IN NEUROLOGY, 2016;
FI: 3,184; Q2
Genetics of Tinnitus: An Emerging Area for Molecular Diagnosis and Drug Development
FRONTIERS IN NEUROSCIENCE, 2016;
FI: 3,398; Q2
A Pilot Study Using Intratympanic Methylprednisolone for Treatment of Persistent Posterior Canal Benign Paroxysmal Positional Vertigo
JOURNAL OF INTERNATIONAL ADVANCED OTOLOGY, 2016;
FI: 0,123; Q4
Generation of human iPSC line GRX-MCiPS4F-A2 from adult peripheral blood mononuclear cells (PBMCs) with Spanish genetic background
STEM CELL RESEARCH, 2015;
FI: 3,693; Q1
Generation and characterization of the human iPSC line PBMC1-iPS4F1 from adult peripheral blood mononuclear cells
STEM CELL RESEARCH, 2015;
FI: 3,693; Q1
Diagnostic criteria for Meniere's disease
JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION, 2015;
FI: 1,19; Q3
Searching for pharmacogenetic targets on Meniere's disease patients
Funder: CURES WITHIN REACH
File number: PS22/047
Execution time: 25/04/2022 - 29/04/2024
Generation and characterization of iPSCs derived from patients with familial Meniere's disease and loss-of-function genetic variants in the MYO7A (MEN7A) gene.
Funder: PUBLIC FOUNDATION FOR BIOSANITARY RESEARCH OF ORIENTAL ANDALUCIA ALEJANDRO OTERO (FIBAO)
File number: INTRAIBS-2021-07
Execution time: 05/02/2022 - 04/02/2023
Neurophysiological bases and safety profile of sound therapy in patients with severe chronic tinnitus (Safe Sound Therapy, SST)
Funder: CARLOS III HEALTH INSTITUTE - FEDER
File number: PI22 / 01838
Execution time: 01/01/2023 - 31/12/2025
IP: PATRICIA PEREZ CARPENA
In Vitro Preclinical ANTI-FN14 Antibody Test and Monitoring of the Clinical Response in Patients with Meniere's Disease (CLIMON)
Funder: MÉNIÈRE'S SOCIETY
File number: MENIERE SOCIETY-2020
Execution time: 01/01/2022 - 31/12/2022
PI: JOSE ANTONIO LOPEZ ESCAMEZ
Genomic profiling for deep phenotyping in patients with early onset Meniere disease (Gen4Phen)
Funder: COUNCIL OF HEALTH AND FAMILIES
File number: PI-0266-2021
Execution time: 09/12/2021 - 08/12/2023
Data Science and Data Infrastructure Program for Personalized Medicine (IMPaCT-Data) of the Precision Medicine Infrastructure Program associated with Science and Technology (IMPaCT)
Funder: CARLOS III HEALTH INSTITUTE - FEDER
File number: IMP/00019-ibs.GRANADA
Execution time: 27/10/2021 - 31/12/2023
PI: JOSE ANTONIO LOPEZ ESCAMEZ
PI20 / 01126 - Cytokines profiling and Multi-omic integrated analysis to re-define clinical phenotypes in Patients With Meniere's disease, Migraine And Vestibular Migraine (Cytomic-Phen)
Funder: CARLOS III HEALTH INSTITUTE - FEDER
File number: PI20 / 01126
Execution time: 01/01/2021 - 31/12/2023
PI: JOSE ANTONIO LOPEZ ESCAMEZ
PRO INFLAMMATORY CYTOKINES AND EPIGENETIC SIGNATURE TO IMPROVE MOLECULAR DIAGNOSIS AND PERSONALIZED MEDICINE IN PATIENTS WITH EPISODE VERTIGO AND MIGRAINE (EPIVERT)
Funder: COUNCIL OF HEALTH AND FAMILIES
File number: PI-0027-2020
Execution time: 01/01/2021 - 31/12/2023
PI: JOSE ANTONIO LOPEZ ESCAMEZ
HEARING 2016 - Identification of novel variants in familial Meniere's disease by whole-genome sequencing
Funder: ACTION ON HEARING LOSS
File number: HEARING-2016-F69
Execution time: 01/09/2016 - 31/10/2016
IP: HEARING 2016 - Identification of novel variants in familial Meniere's disease by whole-genome sequencing
MENIERE SOCIETY 2016-2017 LOPEZ ESCAMEZ
Funder: MÉNIÈRE'S SOCIETY
File number: MENIERE SOCIETY 2016-2017
Execution time: 01/09/2016 - 31/08/2017
PI: JOSE ANTONIO LOPEZ ESCAMEZ
Validation of a genetic marker regulator of inflammation for the diagnosis of autoimmune Meniere's disease (DIEMA)
Funder: PUBLIC FOUNDATION FOR BIOSANITARY RESEARCH OF ORIENTAL ANDALUCIA ALEJANDRO OTERO (FIBAO)
File number: INB-0007
Execution time: 10/06/2017 - 10/06/2019
PI: Validation of a genetic marker regulator of inflammation for the diagnosis of autoimmune Meniere's disease (DIEMA)
Validation of Genetic Markers for the Diagnosis of Autoimmune Meniere's Disease (Diema)
Funder: COUNCIL OF HEALTH
File number: PIN-0105-2017
Execution time: 01/01/2018 - 31/12/2020
PI: JOSE ANTONIO LOPEZ ESCAMEZ
Role of the regulatory variant rs4947296 and the proinflammatory response in Meniere's disease
Funder: CARLOS III HEALTH INSTITUTE - FEDER
File number: PI17 / 01644
Execution time: 01/01/2018 - 31/12/2020
PI: JOSE ANTONIO LOPEZ ESCAMEZ
TIGER - The combined role of genetic and environmental risk factors in the gender-specific development of severe tinnitus
Funder: LA CAIXA FOUNDATION
File number: GENDERNET2018-007
Execution time: 01/01/2019 - 31/12/2021
PI: JOSE ANTONIO LOPEZ ESCAMEZ
IN VITRO CLINICAL TRIAL WITH BIIB023 AND MONITORING OF CLINICAL RESPONSE IN MENIERE DISEASE (CLIMON-MD)
Funder: PUBLIC FOUNDATION FOR BIOSANITARY RESEARCH OF ORIENTAL ANDALUCIA ALEJANDRO OTERO (FIBAO)
File number: PE-0356-2018
Execution time: 01/01/2019 - 31/12/2022
PI: JOSE ANTONIO LOPEZ ESCAMEZ
UNITI - Unification of treatments and Interventions for Tinnitus patients
Funder: EUROPEAN COMMISSION
File number: UNITI H2020
Execution time: 01/01/2020 - 31/12/2022
PI: JOSE ANTONIO LOPEZ ESCAMEZ
ENLIGHTEN 1: A Phase III, Randomized, Blinded, Parallel-Group, Controlled Trial to Evaluate the Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis (CRS) in Adults
Funder: LYRA THERAPEUTICS INC
Type of test: CLINICAL TRIAL WITH DRUGS
Execution time: 27/10/2022 - 30/01/2024
IP: MARIA JESUS MARTINEZ MARTINEZ
Multicenter, three-arm, double-blind, double-masked, parallel-group, placebo-controlled study for the evaluation of the efficacy and safety of the extended-release formulation of betahistine PR 48 mg once daily compared to the formulation of Conventional release of betahistine IR 24 mg, twice daily in the treatment of adult patients with Meniere's disease. BERTIGO
Funder: INTAS PHARMACEUTICALS LTD
Type of test: COMMERCIAL CLINICAL TRIAL
Execution time: 16/03/2022 - 30/04/2024
IP: JUAN MANUEL ESPINOSA SANCHEZ
Multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 2 SENS-111 dosage regimens (100mg and 200mg) administered orally for 4 days in patients suffering from acute unilateral vestibulopathy.
Funder: 4SENSORION
Type of test: COMMERCIAL CLINICAL TRIAL
Execution time: 17/09/2018 - 30/09/2019
PI: JOSE ANTONIO LOPEZ ESCAMEZ
