Research Group on Neurobiology and Molecular Physiopathology in Rare Diseases – NeuroFisER

Metabolism and Organic Damage Area

Rare diseases, also known as minority or orphan diseases, are a group of pathologies with a great heterogeneity. They affect a small number of individuals, which are, in most cases, disabling and even fatal, suffering from an important lack of resources for their treatment.
Our main field of study are neuromuscular diseases, and especially ataxias. Our principal objective is to determine the molecular mechanisms underlying these diseases. Thus, our group we is mainly interested in two types of ataxias: Friedreich’s ataxia (FRDA) and CANVAS Syndrome (Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome).

FRDA is the most frequent clinical form of hereditary ataxias. Understanding the pathophysiology of the disease at the molecular level allows us to identify new therapeutic targets to implement more effective treatments than the current ones for Friedreich’s ataxia. To this end, we study the pathophysiology of the disease using different models. In addition, we are focused on developing new advanced gene therapy strategies using the CRISPR/Cas9 system.

The most recent line of research treats with CANVAS syndrome, a recently diagnosed disabling neurological disease. Our study comprises the generation of iPSCs from skin biopsies of CANVAS patients, and their subsequent differentiation to sensory neurons to obtain a working model. The characterization of the neurons obtained, together with the genetic and clinical screening carried out by our collaborators, will allow us to better understand the pathophysiology of this disease.

Finally, we are developing a line of research focused on Huntington’s disease, where we generate a series of tools to reduce the levels of mutant huntingtin as a therapeutic approach to modify the progress of the disease. Specifically, we are using nanobodies, which are the single-chain variable region of camelid antibodies, fused to ubiquitin ligase domains. This proof of concept consists of obtaining the nanobodies as therapeutic molecules with the capacity to target the mutant huntingtin towards the proteasome for its degradation.

Dra. Pilar González Cabo
Dra. Pilar González Cabo

Leading, R4
Established, R3

Pilar González Cabo    

Recognised/Emerging, R2
First Stage, R1

Laura Robles Rodríguez

Collaborating Researchers
Administrative assistant
CIBERER: Spanish national network for research on rare diseases: a highly productive collaborative initiative. Luque J, Mendes I, Gomez B, Morte B, de Heredia M, Herreras E, Corrochano V, Bueren J, Gallano P, Artuch R, Fillat C, Perez-Jurado L, Montoliu L, Carracedo A, Millan J, Webb S, Palau F, Lapunzina P, Pallardo Calatayud F, CIBERER Network. Clinical Genetics. 2022 May;101(5-6):481-493. doi: 10.1111/cge.14113. PMID: 35060122

Therapeutic strategies targeting mitochondrial calcium signaling: a new hope for neurological diseases?. Rodríguez LR, Lapeña-Luzón T, Benetó N, Beltran-Beltran V, Pallardó FV, Gonzalez-Cabo P, Navarro JA. Antioxidants. 2022 Jan 15;11(1):165. doi: 10.3390/antiox11010165. PMID: 35052668

Cofilin and neurodegeneration: new functions for an old but gold protein. Lapena-Luzon T, Rodriguez L, Beltran-Beltran V, Beneto N, Pallardo F, Gonzalez-Cabo P. Brain Sciences. 2021 Jul 20;11(7):954. doi: 10.3390/brainsci11070954. PMID: 34356188

Friedreich Ataxia: current state-of-the-art, and future prospects for mitochondrial-focused therapies. Pallardo Calatayud F, Pagano G, Rodriguez Melguizo L, González Cabo P, Lyakhovich A, Trifuoggi M. Translational Research. 2021 Mar;229:135-141. doi: 10.1016/j.trsl.2020.08.009. PMID: 32841735

Role of adenosine receptors in rare neurodegenerative diseases with motor symptoms. Beltran-Beltran V, Beneto N, Lapena-Luzon T, Rodriguez LR, Pallardo FV, Gonzalez-Cabo P. Current Protein & Peptide Science. 2021 Dec 27;22(9):675-694. doi: 10.2174/1389203722666210910110126. PMID: 34514988

Antioxidant Therapies and Oxidative Stress in Friedreichs Ataxia: The Right Path or Just a Diversion?. Rodriguez Melguizo L, Lapeña Luzón T, Calap Quintana P, Moltó Ruiz M, González Cabo P, Navarro Langa J. Antioxidants (Basel, Switzerland). 2020 Jul 24;9(8):664. doi: 10.3390/antiox9080664. PMID: 32722309

Cofilin dysregulation alters actin turnover in frataxin-deficient neurons. Muñoz Lasso D, Molla B, Calap Quintana P, Garcia Gimenez J, Pallardo Calatayud F, Palau F, González Cabo P. Scientific Reports. 2020 Mar 23;10(1):5207. doi: 10.1038/s41598-020-62050-7. PMID: 32251310

Much More Than a Scaffold: Cytoskeletal Proteins in Neurological Disorders. Muñoz Lasso D, Roma Mateo C, Pallardo Calatayud F, González Cabo P. Cells. 2020 Feb 4;9(2):358. doi: 10.3390/cells9020358. PMID: 32033020

Oxidative stress modulates rearrangement of endoplasmic reticulum-mitochondria contacts and calcium dysregulation in a Friedreich’s ataxia model. Rodríguez LR, Calap-Quintana P, Lapeña-Luzón T, Pallardó FV, Schneuwly S, Navarro JA, Gonzalez-Cabo P. Redox Biology. 2020 Oct 16;37:101762. doi: 10.1016/j.redox.2020.101762. PMID: 33128998

PPAR gamma agonist leriglitazone improves frataxin-loss impairments in cellular and animal models of Friedreich Ataxia. Rodriguez-Pascau L, Britti E, Calap Quintana P, Dong Y, Vergara C, Delaspre F, Medina M, Tamarit J, Pallardo Calatayud F, González Cabo P, Ros J, Lynch D, Martinell M, Pizcueta P. Neurobiology of Disease. 2020 Nov 7;148:105162. doi: 10.1016/j.nbd.2020.105162. PMID: 33171227

Thioredoxin and Glutaredoxin Systems as Potential Targets for the Development of New Treatments in Friedreich’s Ataxia. Seco-Cervera M, Gonzalez-Cabo P, Pallardo F, Roma-Mateo C, Garcia-Gimenez J. Antioxidants. 2020 Dec 10;9(12):E1257. doi: 10.3390/antiox9121257. PMID: 33321938

Reference: ACCI 2020
Title: Síndrome de CANVAS: diagnóstico precoz y modelo fisiopatológico mediante iPSC.
Funding body: Instituto de Salud Carlos III – Cofinanciado FEDER
Principal Investigator: Pilar González Cabo
Duration: 2021 – 2022
Total budget: 75.000 €
Reference: PID2020-115190RB-I00
Title: Relacionando cofilina, una proteína de unión a actina, con la desregulación del calcio: un enfoque de precisión para el tratamiento de la ataxia de Friedreich
Funding body: Ministerio de Ciencia e Innovación
Principal Investigator: Pilar González Cabo
Duration: 2021 – 2023
Total budget: 196.300 €
Reference: ACCI-2019-22
Title: Degradación de la huntingtina mediante ubiquibodies de camélidos
Funding body: CIBER de Enfermedades Raras (CIBERER-ISCIII)
Principal Investigator: Pilar González Cabo
Duration: 2020 – 2022
Total budget: 18.000 €
Reference: RTC2019-006825-1
Title: Potencial de la leriglitazona para el tratamiento de enfermedades asociadas a la acumulación de hierro, distrofias y enfermedades neuromusculares
Funding body: Ministerio de Ciencia e Innovación
Principal Investigator: Pilar González Cabo
Duration: 2020 – 2023
Total budget: 90.000 €
Reference: ACCI-CIBERER 2018
Title: Edición Génica del Gen FXN mediante el Sistema CRISPR/Cas9 en linfocitos de pacientes con ataxia de Friedreich
Funding body: CIBER de Enfermedades Raras (CIBERER-ISCIII)
Principal Investigator: Pilar González Cabo
Duration: 2019 – 2021
Total budget: 39.750 €