One member of our group, Miguel Molina Berenguer, has defended his PhD thesis consisting in the generation of the first genetically modified murine model of the combined oxidative phosphorylation deficiency 1 (knock-in mouse in the Gfm1). In this frame, we have initiated the development of the project “Generation of therapies and biomarkers for the treatment of mitochondrial dysfunction-driven neurodegenerative diseases (DRUG4-COXPD1)”, funded by the “planes complementarios de biotecnología aplicada a la salud”. This is a coordinated project, and our role in it consists in the development of an AAV-based gene therapy approach for COXPD1.
We identified novel mutations in patients with mitochondrial DNA (mtDNA) maintenance disorders and presence of mtDNA multiple deletions in muscle (genes RRM2B, PMID: 36959467 and TOP3A, PMID: 36544354). This last report is actually the second report associating mutations in TOP3A to multiple mtDNA deletions and progressive external ophthalmoplegia.
eCORE
- Advanced Therapies and Advanced Interventions, Nanomedicine, Transplant & Donation
- Brain & Mind and Behaviour
- Woman & Child Health & Rare Diseases
Team
Group Leader
Ramon Martí Seves
Principal Investigator (PI)
Elena García-Arumí, Tomàs Pinós Figueras, Yolanda Cámara Navarro
Researchers
Maria Jesús Melià Grimal, Miguel Molina Berenguer
PhD Students
Javier Ramón Pasías, Mónica Azucena Villareal Salazar, Andrea Férriz Gordillo, Pau Mollá Zaragozá, Bernat García Adán, Juan Luis Restrepo Vera, Izaskun Izagirre Urizar
Publications
Valenzuela PL, Santalla A, Alejo LB, Merlo A, Bustos A, Castellote-Bellés L, Ferrer-Costa R, Maffiuletti NA, Barranco-Gil D, Pinós T, Lucia A.
Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability: Insights from McArdle disease.
J Sport Health Sci. 2023 Nov 27:S2095-2546(23)00115-1
DOI: 10.1016/j.jshs.2023.11.006
IF: 12.2
Blasco-Pérez L, Iranzo-Nuez L, López-Ortega R, Martínez-Cruz D, Camprodon-Gómez M, Tenés A, Antolín M, Tizzano EF, García-Arumí E
An Integral Approach to the Molecular Diagnosis of Tuberous Sclerosis Complex: The Role of Mosaicism and Splicing Variants
J Mol Diagn. 2023 Sep;25(9):692-701.
DOI: 10.1016/j.jmoldx.2023.06.006
IF: 4.9
Restrepo-Vera JL, Rovira-Moreno E, Ramón J, Codina-Sola M, Llauradó A, Salvadó M, Sánchez-Tejerina D, Sotoca J, Martínez-Sáez E, Martí R, García-Arumí E, Juntas-Morales R
Identification of two novel RRM2B variants associated with autosomal recessive progressive external ophthalmoplegia in a family with pseudodominant inheritance pattern.
J Hum Genet. 2023 Aug;68(8):527-532
DOI: 10.1038/s10038-023-01144-2
IF: 3.545
Llauradó A, Rovira-Moreno E, Codina-Solà M, Martínez-Saez E, Salvadó M, Sanchez-Tejerina D, Sotoca J, López-Diego V, Restrepo-Vera JL, Garcia-Arumi E, Juntas-Morales R.
Chronic progressive external ophthalmoplegia plus syndrome due to homozygous missense variant in TOP3A gene.
Clin Genet. 2023 Apr;103(4):492-494.
DOI: 10.1111/cge.14287
IF: 3.5
Karazi W, Scalco RS, Stemmerik MG, Løkken N, Lucia A, Santalla A, Martinuzzi A, Vavla M, Reni G, Toscano A, Musumeci O, Kouwenberg CV, Laforêt P, Millán BS, Vieitez I, Siciliano G, Kühnle E, Trost R, Sacconi S, Durmus H, Kierdaszuk B, Wakelin A, Andreu AL, Pinós T, Marti R, Quinlivan R, Vissing J, Voermans NC; EUROMAC Consortium
Data from the European registry for patients with McArdle disease (EUROMAC): functional status and social participation.
Orphanet J Rare Dis. 2023 Jul 25;18(1):210
DOI: 10.1186/s13023-023-02825-z
IF: 3.7
Projects
Nueva aproximación a la enfermedad de McArdle: Un enfoque integrador desde los modelos preclínicos hasta la calidad de vida de los pacientes.
Principal Investigator: Tomàs Pinós
Agency: Instituto de Salud Carlos III (Ref. PI22/00201)
Funding: 93,170 €
Period: January 2023 – December 2025
Preclinical efficacy studies for the use of deoxyribonucleosides as a treatment for mitochondrial DNA depletion/multiple deletions syndromes (MDDS). Extension to unexplored genetic causes.
Principal Investigator: Ramon Martí
Agency: Instituto de Salud Carlos III (Ref. PI21/00554)
Funding: 153,670 €
Period: January 2022 – December 2024
Deoxyribonucleosides as a therapy for mitochondrial DNA replication disorders: understanding therapeutic mechanisms and broadening the treatment to mutations in POLG and other related genes.
Principal Investigator: Ramon Martí
Agency: Fundació La Marató de TV3
Funding: 296,375 €
Period: May 2021 – December 2024
Mitochondrial respiratory complex I at the interface between oxidative metabolism and nucleotide homeostasis
Principal Investigator: Yolanda Cámara
Agency: Ministerio de Ciencia e Innovación
Funding: 157,300 €
Period: September 2021 - August 2024
Desarrollo de una estrategia de terapia génica para la deficiencia combinada de la fosforilación oxidativa tipo 1 debido a mutaciones en GFM1.
Principal Investigator: Ramon Martí
Agency: Fundación Mutua Madrileña
Funding: 150,000 €
Period: July 2021 – June 2024
Patents
DEOXYNUCLEOSIDE THERAPY FOR DISEASES CAUSED BY UNBALANCED NUCLEOTIDE POOLS INCLUDING MITOCHONDRIAL DNA DEPLETION SYNDROMES
Priority Number: PCT/US2016/038110
Priority Date: 17/06/2015
Applicants: Michio Hirano, Caterina Garone, Ramon Martí
TREATMENT OF MITOCHONDRIAL DISEASES
Priority Number: PCT/EP2016/062636
Priority Date: 05/06/2015
Applicants: Ramon Martí, Emiliano González, Cora Blázquez, Javier Torres, Raquel Cabrera, Yolanda Cámara
