Research

About

The Group of Research in Neuromuscular Diseases from Badalona (GRENBA) has a mixed format and is made up of clinical staff from the Neurology and Paediatric services at the Germans Trias i Pujol University Hospital and specialised basic researchers in the laboratory at IGTP.

This multidisciplinary team has the main objective of searching for solutions for neuromuscular patients. To achieve this, the team relies on its extensive clinical expertise in the diagnosis and management of these patients, and it has recently built a powerful patient database.

In the laboratory, the team has extensive expertise in genetic, epigenetic, transcriptomic and proteomic techniques to study the pathogenicity of prevalent neuromuscular diseases such as Myotonic Dystrophy type I, Glycogenosis type V and Duchenne Muscular Dystrophy, at the molecular level. The team is also experienced in generating cellular models derived from patients and in testing treatments in vitro, in vivo and in patients. Additionally, the researchers work on many collaborative projects with national and international investigators also involved in the study of these pathologies.

Keywords: Neuromuscular disorders, neurology, paediatrics, muscle regeneration, pathological mechanisms.

Group of Research in Neuromuscular Diseases from Badalona (GRENBA)

Research lines

Myotonic Dystrophy type I

Myotonic dystrophy type I (DM1, also known as Steinert's disease) is the most prevalent dystrophy in adults (cases are 1:8000). Patients present a genetic defect, which affects many tissues and organs of the body. In the more severe cases, the congenital forms, patients' quality of life is severely compromised with affectation of the central nervous system. Today there is no treatment to stop the progression of this disease. Currently, the team are working in two areas of research: 1) testing in vitro the therapeutic value that antisense oligonucleotides can offer to these patients; 2) identifying new biomarkers with clinical applications for diagnosis, prevention of symptoms and/or treatment follow up.

McArdle Disease or Glycogenosis type V

McArdle disease is a metabolic disease which has genetic causes. Patients present exercise intolerance with contractures and myalgias. In this line of research, the group is optimizing the genetic diagnosis strategies for this disorder. Additionally, they are evaluating exercise interventions for these patients, as it can have a serious impact on well-being and improve quality of life.

Epigenetic changes in muscle pathologies

Epigenetic alterations have profound effects on human pathologies, because histone modifications and DNA methylation influence gene expression. In the laboratory, the team are characterizing epigenetic profiles that could be altered in prevalent muscular dystrophies, such as DM1 and DM2, and in rhabdomyosarcomas.

Myotonic Dystrophy type II

Myotonic dystrophy type II has a similar genetic defect to Myotonic dystrophy type I, however the prevalence is lower and patients have milder presentation. In recent years, the new cases of myotonic dystrophy type II described have shown that there are many patients who have a non-classic debut symptomatology and that many cases remain undiagnosed. The aims of this line of research are to cover a broader range of symptomatic patients and to diagnose new myotonic dystrophy type II cases as well as to better define their clinical characteristics.

Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy in childhood, with a prevalence of 1 in 3500 boys world-wide. DMD is a genetic disorder characterized by a continued muscle degeneration, progressive muscle weakness, impaired locomotion and premature death by respiratory and cardiac failures. Unfortunately, DMD is an incurable disease and patients can only receive palliative therapies to delay symptoms and disease progression. There is no doubt that new therapeutical targets are needed to treat this devastating disease.  Based on previous results of our group, we envision HDAC11 as a new potential therapeutic target for DMD and in the lab we are exploring deeply the role of HDAC11 in the pathological context of muscle dystrophies. 

Deciphering the role of HDAC11 in skeletal muscle homeostasis, regeneration and muscular dystrophies

Active projects

DM1-Heart: Searching biomarkers of heart damage in Myotonic Dystrophy type 1 patients

PI: Gisela Nogales
Funding agency: Instituto de Salud Carlos III (ISCII)
Agency code: PI22/00104
Start date: 01/01/2023
End date: 31/12/2025

DIMINUTOS, Childhood and adult myotonic dystrophy: evaluation of new treatments and pathogenicity through genetic, epigenetic and molecular imaging analysis

PI: Gisela Nogales
Funding agency: Instituto de Salud Carlos III (ISCII)
Agency code: PI18/000713
Start date: 01/01/2019
End date: 30/06/2023

Exploring HDAC11 functions in muscular dystrophies

PI: Mònica Suelves
Funding agency: Ministerio de Ciencia e Innovación (MICINN)
Agency code: PID2020-118730RB-I00
Start date: 01/01/2021
End date: 31/12/2024

Exploring HDAC11 functions in Duchenne muscular dystrophy

PI: Mònica Suelves
Funding agency: AFM Telethon
Agency code: 23557
Start date: 15/09/2021
End date: 30/01/2024

Scientific publications

Villarreal-Salazar M, Brull A, Nogales-Gadea G, Andreu AL, Martín MA, Arenas J, Santalla A, Lucia A, Vissing J, Krag TO, Pinós T. Preclinical Research in McArdle Disease: A Review of Research Models and Therapeutic Strategies. Genes (Basel). 2021 Dec 28;13(1):74. DOI: 10.3390/genes13010074.

Lucia A, Martinuzzi A, Nogales-Gadea G, Quinlivan R, Reason S; International Association for Muscle Glycogen Storage Disease study group. Clinical practice guidelines for glycogen storage disease V & VII (McArdle disease and Tarui disease) from an international study group. Neuromuscul Disord. 2021 Dec;31(12):1296-1310. DOI: 10.1016/j.nmd.2021.10.006. Erratum in: Neuromuscul Disord. 2022 Feb 6.

García-Consuegra I, Asensio-Peña S, Garrido-Moraga R, Pinós T, Domínguez-González C, Santalla A, Nogales-Gadea G, Serrano-Lorenzo P, Andreu AL, Arenas J, Zugaza JL, Lucia A, Martín MA. Identification of Potential Muscle Biomarkers in McArdle Disease: Insights from Muscle Proteome Analysis. Int J Mol Sci. 2022 Apr 22;23(9):4650. DOI: 10.3390/ijms23094650.

Koehorst E, Odria R, Capó J, Núñez-Manchón J, Arbex A, Almendrote M, Linares-Pardo I, Natera-de Benito D, Saez V, Nascimento A, Ortez C, Rubio MÁ, Díaz-Manera J, Alonso-Pérez J, Lucente G, Rodriguez-Palmero A, Ramos-Fransi A, Martínez-Piñeiro A, Nogales-Gadea G, Suelves M. An Integrative Analysis of DNA Methylation Pattern in Myotonic Dystrophy Type 1 Samples Reveals a Distinct DNA Methylation Profile between Tissues and a Novel Muscle-Associated Epigenetic Dysregulation. Biomedicines. 2022 Jun 10;10(6):1372. DOI: 10.3390/biomedicines10061372.

Santalla A, Valenzuela PL, Rodriguez-Lopez C, Rodríguez-Gómez I, Nogales-Gadea G, Pinós T, Arenas J, Martín MA, Santos-Lozano A, Morán M, Fiuza-Luces C, Ara I, Lucia A. Long-Term Exercise Intervention in Patients with McArdle Disease: Clinical and Aerobic Fitness Benefits. Med Sci Sports Exerc. 2022 Aug 1;54(8):1231-1241. DOI: 10.1249/MSS.0000000000002915.

López A, Soblechero P, Catalli C, Jauregui A, Kapetanovic S, Nogales G, Arechavala V. Characterisation of cell culture models of myotonic dystrophy type I by In-Cell Western technology and digital droplet PCR. Neuromuscul Disord. 2022 Oct;32(1):132-133. DOI: 10.1016/j.nmd.2022.07.377.

García-Puga M, Saenz-Antoñanzas A, Gerenu G, Arrieta-Legorburu A, Fernández-Torrón R, Zulaica M, Saenz A, Elizazu J, Nogales-Gadea G, Gadalla SM, Araúzo-Bravo MJ, López de Munain A, Matheu A. Senescence plays a role in myotonic dystrophy type 1. JCI Insight. 2022 Oct 10;7(19):e159357. DOI: 10.1172/jci.insight.159357.

Villarreal-Salazar M, Santalla A, Real-Martínez A, Nogales-Gadea G, Valenzuela PL, Fiuza-Luces C, Andreu AL, Rodríguez-Aguilera JC, Martín MA, Arenas J, Vissing J, Lucia A, Krag TO, Pinós T. Low aerobic capacity in McArdle disease: A role for mitochondrial network impairment? Mol Metab. 2022 Dec;66:101648. DOI: 10.1016/j.molmet.2022.101648.

Gisela Nogales’ PUBLICATIONS

Alicia Martínez’s publications

Mònica Suelves’ publications

alba Ramos’ publications

Additional information

The Group of Research in Neuromuscular Diseases from Badalona unveils its new logo

(May 2023) The group previously known as Neuromuscular and Neuropediatric Research Group has updated its name to Group of REsearch in Neuromuscular diseases from BAdalona (GRENBA) and has created its own logo. For the design process, students from the Escola d'Art Superior Pau Gargallo, Badalona, visited the research group at IGTP and presented various proposals. Choosing the logo was a challenge, as many were highly creative and well-designed, but in the end, Melissa Abigail Alava Mieles' design emerged as the winner. The research group would like to thank all students for their involvement in this project, as well as professors Miquel Aregay, Montserrat Sayol, and Júlia Cuyàs.

Dr Gisela Nogales Gadea Awarded Consolidation Researcher Program 2022

(June 2023) The Ministry of Innovation and Science has awarded the Consolidation Researcher Programme 2022 to Dr Gisela Nogales Gadea, leader of the Group of Research in Neuromuscular Diseases from Badalona (GRENBA) at IGTP. This competitive programme, included within the State Programme to Develop, Attract, and Retain Talent of the State Plan (and funded with European funds from the Recovery, Transformation, and Resilience Plan), aims to promote the consolidation of the research career of investigators, encouraging the creation of permanent positions in the affiliated institutions and facilitating the strengthening of the research line through the funding of a project of their own. Dr Nogales started GRENBA in 2015, together with clinical staff from the neuromuscular unit of the Neurology Service and the neuropaediatrics unit of the Paediatrics Service of the HUGTiP, within the framework of a Miguel Servet programme funded by the Carlos III Health Institute. The award of this programme represents a new boost for this team, as it allows the incorporation of Dr Nogales as IGTP staff, and funding for a research project, in which third-generation genetic sequencing technology will be implemented to improve the diagnosis, prognosis, and response to therapy of patients with Myotonic Dystrophy type 1.

News

Thirteen researchers from IGTP bring science closer to students in the 6th edition of #100tífiques

On 7 February, "#100tífiques" returned for its sixth edition, a macro-event that has become a benchmark for advocacy within the Catalan female research community and schools. Expanding on last year's participant numbers, thirteen scientists from IGTP took part in this event.

- Projects

Four IGTP projects financed with 1.7 million euros by the Spanish Ministry of Science and Innovation

The Germans Trias i Pujol Research Institute (IGTP) has received funding to develop four projects as part of the "Public-Private Collaboration Projects" call by the State Research Agency of the Ministry of Science and Innovation, amounting to a total of €1,706,019.92.

+ News