About
The Neurogenetics Research Unit was founded by Dr Antoni Matilla in 2009. It is located at the Can Ruti Campus and is integrated within the Department of Neurosciences at Germans Trias i Pujol University Hospital (HUGTiP). The unit also provides genetics diagnoses to the Neurology and Paediatrics Services at HUGTiP and to other centres in Spain and abroad.
The group studies the genetic bases and molecular mechanisms underlying neurodegenerative processes. The ultimate goal of their research is to identify disease causative and modifying genes, their products and the molecular pathways involved in the function and dysfunction of the nervous system to effectively provide genetic diagnosis and identify selective therapeutic approaches for patients. To achieve this, the team uses multidisciplinary approaches including next-generation and long-molecule nanopore DNA and RNA sequencing, functional studies, biochemical, epigenomics, proteomics, transcriptomics, and molecular neurosignaling studies. Scientists in the unit develop large-scale genomics technologies and bioinformatics tools to identify genetic causes underlying neurological diseases.
An important and strategic objective of the unit is to identify and implement treatments for various neurodegenerative diseases. To that end, Drs Antoni Matilla and Ivelisse Sanchez established the functional biology and experimental therapies laboratory at IGTP’s Neurogenetics Unit in 2015. The laboratory uses advanced gene therapy technology based on adenoassociated virus vectors (AAV), screenings of drug compounds and genetic libraries, and in vitro and in vivo preclinical testing of new therapeutic candidates. The group is currently developing an AAV-based gene therapy for the treatment of Friedreich's ataxia. To further develop and implement this gene therapy for Friedreich's Ataxia in patients, Drs Antoni Matilla and Sanchez established the spin-off Biointaxis in 2018.
Keywords: Ataxias, Adenoassociated Viral Vectors (AAV), advanced therapies, cell death, disease biomarkers, gene therapy, genomics, neurodegeneration, neurogenetics, paraplegias.
Group leader
- Antoni Matilla Dueñas, PhD
Antoni Matilla Dueñas, PhD
Born in Barcelona, Spain, Antoni Matilla studied Biological Sciences specialising in Genetics and Molecular Biology in the University of Barcelona (1986). He gained his PhD in 1995 on Biochemistry, Genetics, Molecular Biology and Neuroscience on the investigation of the genetic and molecular mechanisms of neurodegeneration in inherited ataxias. He completed his PhD at Baylor College of Medicine in Houston, USA (1995) and obtained a fellowship from the Spanish Research Council to pursue a post-doctoral stage at Baylor College. After a short stay at the Rockefeller University in New York, in 1998, Dr Matilla was granted with a post-doctoral fellowship from the Howard Hughes Medical Institute in the USA to complete his post-doctoral studies at the Eccles Institute of Human Genetics of the University of Utah, in Salt Lake City. From 2000 to 2007, he was senior lecturer/research group leader at the Institute of Child Health of the University College London, where he established his own research group. In 2008, he established the Neurogenetics Unit at the Germans Trias i Pujol Research Institute (IGTP) in Badalona, Spain, currently formed by 13 members. The main research interests are the elucidation of the molecular basis of neurodegeneration in inherited ataxias with the aim of identifying and implementing treatments. Dr Matilla has published more than 60 original scientific publications in excellent international journals (Total impact factor: 404; 2,815 citations) and given more than 130 lectures in Spain and abroad. He has obtained overall funding for 6.9M euros.
Dr Matilla was a member of the Scientific Advisory Board of RARE-bestpractices and associate member of NEUROMICS, both consortiums funded by the 7th FP of the European Commission (2013-2017). From 2004 to 2009, he was appointed as scientific coordinator of the EUROSCA project on ataxias also funded by the European Commission. From 2010 to 2013, he coordinated the Ibero-American network for the multidisciplinary study of Parkinson's Disease and spinocerebellar ataxias (RIBERMOV) funded by the Ibero-American Program of Science and Technology for Development (CYTED). Dr Matilla is a co-founder member of the European Ataxia Study Group and a current active member of the international Ataxia Global Initiative. He is a peer-reviewer of scientific manuscripts for more than 30 scientific journals, and evaluates projects as a scientific expert for national and international government and private funding agencies including AEI, AGAUR, Ataxia-UK, the European Commission, the Israel Science Foundation, UK Medical Research Council, the Italian Telemarathon and the Hong Kong Government Health Agency. He is or has been a member of the Scientific Committees of Spanish (FEDAES), Catalan (ACAH), and European (Euro-Ataxia) Patient Associations of which he has also been a member of the Executive Directors Committee. From 2005 to 2017, he was head editor of the Genetics Section of The Cerebellum (Springer). Dr Matilla is accredited since 2001 in Human Genetics by the Spanish Association of Human Genetics and teaches in several post-graduate programs on Human Genetics and Genetic Counseling. He has several licenses with industry and 12 international patents currently active. In 2018, he co-founded Biointaxis S.L., a spin-off dedicated to developing and implement a gene therapy curative treatment for Friedreich's ataxia.
Contact: amatilla(ELIMINAR)@igtp.cat
ORCID: 0000-0002-3514-4181 - Ivelisse Sánchez Díaz, PhD
Team
Post-doctoral investigators
Eudald Balagué Cabasés, PhD(ELIMINAR)
Marc Corral Juan, PhD(ELIMINAR)
PhD student
Natalia Benitez Calle(ELIMINAR)
MSc students
Gabriela Chabrzyk
Nicolás Llanes Vizcaíno
Undergraduate students
Marc Sans Falip
Lab manager
Daniel Cota González (ELIMINAR)
Research assistants
Aleix Folch Guillen(ELIMINAR)
Nerea Ramírez Martínez(ELIMINAR)
Technician
Esther Gasch Navalón(ELIMINAR)
Administrative assistant
Rafael Cantarero Osorio(ELIMINAR)
Research lines
- Identification of the genetic causative deficits and the molecular mechanisms underlying hereditary ataxias, spastic paraplegias and other neurodegenerative disorders
- Genetic diagnosis of over 400 neurological diseases
- Multiomics-based identification of biomarkers of disease progression in hereditary ataxias and other neurodegenerative disorders
- Defining clinical-genetic-molecular correlations implementing machine learning
- Identification of signaling targets and therapeutic strategies for neurological disorders in cellular and animal disease models
- Development of a gene therapy for Friedreich Ataxia and its evaluation in mouse models of the disease
Active projects
Industrial Doctorate. Gene therapy for Friedreich's ataxia
Funding agency: Agència de Gestió d'Ajuts Universitaris (AGAUR)
Agency code: 2022 DI 102
Duration: 2023 - 2026
ISCIII-CDTI de Innovaciones en medicina personalizada y terapias avanzadas: Gene therapy for Friedreich's ataxia
PI: Antoni Matilla-Dueñas, Ivelisse Sánchez
Funding agency: Centro para el Desarrollo Tecnológico Industrial (CDTI), Instituto de Salud Carlos III (ISCIII)
Agency code: PMPTA22/00018; IDI-20230057
Duration: 2023 - 2024
Pre-clinical validation of a novel gene therapy for a rare disease in non-human primates: integrative approach to the CMC scale-up process validation of a gene therapy product for Friedreich Ataxia
Funding agency: European Commission
Agency code: WomenTech 101114192
Duration: 2023 - 2024
Neurogenetics and Neurodegenerative Diseases Consolidated Research Group
Funding agency: Agència de Gestió d'Ajuts Universitaris (AGAUR)
Agency code: 2021 SGR 00541
Duration: 2023 - 2025
Gene therapy for Friedreich's Ataxia
Funding agency: Fundación Inocente/STOP-FA
Duration: 2024 – 2025
Industrial Doctorate. Gene therapy for Friedreich's ataxia
Funding agency: Spanish Ministry of Science and Innovation
Agency code: DIN2022-012509
Duration: 2023 - 2027
A first-in-class AAV-gene therapy for the curative treatment of Friedreich's Ataxia
PI: Antoni Matilla-Dueñas
Funding agency: Fundación "La Caixa"
Agency code: CL91-00017
Duration: 2020 - 2024
Past projects
Preclinical evaluation of a new gene therapy vector based on adenoassociated virus in the reversion of the neurological and cardiac signs in an acute mouse model with Friedreich's ataxia
PI: Antoni Matilla-Dueñas. Co-PI: Ivelisse Sánchez
Funding agency: Instituto de Salud Carlos III (ISCIII)
Agency code: PI20/00647
Duration: 2021 - 2023
Development of an innovative gene therapy drug for the treatment of Friedreich's Ataxia
PI: Antoni Matilla-Dueñas
Funding agency: Ministerio de Ciencia e Innovación Retos-Colaboración
Agency code: RTC2019-006995-1
Duration: 2020 - 2023
Biointaxis S.L. business plan: development of FRATAXAV, a gene therapy drug based on adeno-associated virus AAV to treat Friedreich's ataxia
Funding agency: Centro para el Desarrollo Tecnológico Industrial (CDTI)
Agency code: EXP-00123449/SNEO-20191074
Duration: 2020 - 2022
Scientific publications
Highlighted publications
Sanchez-Flores M, Corral-Juan M, Gasch-Navalón E, Cirillo D, Sanchez I, Matilla-Dueñas A. Novel genotype-phenotype correlations, differential cerebellar allele-specific methylation, and a common origin of the (ATTTC)n insertion in spinocerebellar ataxia type 37. Hum Genet. 2024 Mar;143(3):211-232. DOI: 10.1007/s00439-024-02644-7.
Corral-Juan M, Casquero P, Giraldo-Restrepo N, Laurie S, Martinez-Piñeiro A, Mateo-Montero RC, Ispierto L, Vilas D, Tolosa E, Volpini V, Alvarez-Ramo R, Sánchez I, Matilla-Dueñas A. New spinocerebellar ataxia subtype caused by SAMD9L mutation triggering mitochondrial dysregulation (SCA49). Brain Commun. 2022 Feb 10;4(2):fcac030. DOI: 10.1093/braincomms/fcac030.
Matilla-Dueñas A, Infante J, Serrano-Munuera C, Ivánovic-Barbeito Y, Alvarez R, Sánchez I. Novel Therapeutic Challenges in Cerebellar Diseases. Handbook of the Cerebellum and Cerebellar Disorders. 2021 Dec 5;2667-2699. DOI: 10.1007/978-3-030-23810-0_106
Corral-Juan M, Serrano-Munuera C, Rábano A, Cota-González D, Segarra-Roca A, Ispierto L, Cano-Orgaz AT, Adarmes AD, Méndez-Del-Barrio C, Jesús S, Mir P, Volpini V, Alvarez-Ramo R, Sánchez I, Matilla-Dueñas A. Clinical, genetic and neuropathological characterization of spinocerebellar ataxia type 37. Brain. 2018 Jul 1;141(7):1981-1997. DOI: 10.1093/brain/awy137.
Serrano-Munuera C, Corral-Juan M, Stevanin G, San Nicolás H, Roig C, Corral J, Campos B, de Jorge L, Morcillo-Suárez C, Navarro A, Forlani S, Durr A, Kulisevsky J, Brice A, Sánchez I, Volpini V, Matilla-Dueñas A. New subtype of spinocerebellar ataxia with altered vertical eye movements mapping to chromosome 1p32. JAMA Neurol. 2013 Jun;70(6):764-71. DOI: 10.1001/jamaneurol.2013.2311.
Additional information
Collaborative networks
International Ataxia Global Initiative (AGI). More information
Doctoral theses
Title: Pre-clinical evaluation of two candidate recombinant vectors for the gene therapy treatment of Friedreich's ataxia and identification of relevant clinical biomarkers
Author: Natalia Benitez Calle
University: Universitat Autònoma de Barcelona
Currently in progress
Master’s theses
Title: Genetic, cellular and molecular insights into VPS13D-ataxia
Author: Gabriela Chabrzyk
University: Universitat Autònoma de Barcelona
Currently in progress
Title: Characterization of the biodistribution of recombinant frataxin protein in the Friedreich ataxia mouse model treated with AAV-FXN gene therapy
Author: José Cánovas Marín
University: Universitat Autònoma de Barcelona
Date of defence: 2023
Title: A new CRISPRCas9 target sequence enrichment for the analysis of the expanded region in FXN, its methylation profile and expression
Author: Natalia Benitez Calle
University: Universitat Autònoma de Barcelona
Date of defence: 2022
Title: Transcriptomic biomarkers of disease progression in Friedreich Ataxia
Author: Nicolás Llanes Vizcaíno
University: University of Barcelona
Currently in progress
Title: Undiagnosed inherited ataxias: identification of a novel spinocerebellar ataxia subtype
Author: Nerea Ramírez Martínez
University: Universitat Pompeu Fabra
Date of defence: 2023
Title: Targeted nanopore sequencing of the SCA37 (ATTTC)n expanded insertion within the DAB1 gene proves a common origin and differential methylation
Author: Marina Sánchez Flores
University: University of Barcelona
Date of defence: 2022
Biointaxis
Biointaxis is a recently created academic Biotech spin-off from the Germans Trias i Pujol Research Institute (IGTP). The team is led by Dr Matilla and Dr Sánchez, both pioneers in the identification of ataxia genes and research in neurodegenerative disorders. They are currently developing a gene therapy treatment for Friedreich´s ataxia, a rare inherited, progressive, neurodegenerative disease that typically affects teenagers and young adults. Their research shows efficacy of the treatment being able to re-establish the neurological functions in mice models of Friedreich’s ataxia. They develop life-changing treatments for rare genetic diseases such as Friedreich's ataxia.
News
Scientists use an innovative approach to provide relevant insights into a rare neurologic disorder
Researchers from IGTP and BSC-CNS have discovered new genetic mechanisms related to spinocerebellar ataxia type 37. Their research, published in the journal Human Genetics, employed advanced techniques such as CRISPR/Cas9 gene editing, real-time large DNA sequencing and machine learning. The study deepens our understanding of this inherited disease, leading to more precise diagnoses and improved genetic counselling for patients.
State funding of €1.8M to develop an advanced gene therapy for Friedreich's ataxia
The Centre for the Development of Industrial Technology (CDTI) and the Carlos III Health Institute (ISCII) will fund the project with 1.8 million euros within the R&D&I call linked to Personalised Medicine and Advanced Therapies in the framework of the Strategic Project for the Recovery and Economic Transformation for Vanguard Health (PERTE for Vanguard Health) in gene therapy for Friedreich's ataxia.
Contact
Antoni Matilla
(+34) 93 033 05 32
More links
Donate via Amics de Can Ruti · Follow @AntoniMatilla on X · Follow @NG_IGTP on X · Biointaxis