Researchers from the IIS La Fe and the CIBERER develop a potential treatment for the rare muscular dystrophy LGMD D2 with gene editing

Researchers at the La Fe Health Research Institute (IIS La Fe) and the Centre for Biomedical Research Network on Rare Diseases (CIBERER) have managed to correct the mutation of the gene that causes LGMD D2 muscular dystrophy in cells from patients affected by this disorder, also known as transportin muscular dystrophy, using CRISPR-Cas9 gene-editing technology. Of the approximately 100 cases of this rare disease known worldwide, 90 are in Spain. The results of this research are presented as a potential treatment for this disease.

The gene carrying the disease-causing mutation (TNPO3) encodes a protein that is responsible for introducing other proteins related to nucleic acid metabolism into the cell nucleus and is also involved in other diseases such as HIV infection (AIDS). The study was carried out on immortalised muscle cells from a patient suffering from the disease. The research, published in the journal Molecular Therapy - Nucleic Acids, showed that the treated diseased cells regained vitality, corrected several altered functions such as autophagy and largely recovered previously altered cell function.

The European Reference Unit for Rare Neuromuscular Diseases of the Hospital Universitari i Politècnic La Fe de València, the Neuromuscular Pathology Research Group of the IIS La Fe and the Molecular, Cellular and Genomic Biomedicine Unit of the same institute, both integrated in the Centre for Biomedical Research Network on Rare Diseases (CIBERER), have collaborated in the research. Researchers from the Institute of Biotechnology and Biomedicine (BIOTECMED) of the University of Valencia have also participated.

On LGMD D2 muscular dystrophy

LGMD D2 muscular dystrophy is an ultra-rare disease with a special incidence in Spain. The 90 cases diagnosed in our country belong to a lineage whose common ancestor lived 8 generations ago in a village in the interior of the region of Murcia. The disease is basically characterised by progressive muscular paralysis with a wide variability regarding age of onset, evolution and severity. "The pathogenic mechanisms of this disease are unknown, but this study may help to discover them," stresses the coordinator of the study, Juan Jesús Vílchez, a researcher at IIS La Fe and CIBERER.

This research has received substantial funding from the Conquistando Escalones Association of patients with this disease. For its start-up, the project also received aid from the CIBERER's Intramural Cooperative Collaborative Intramural Actions (ACCI) programme. Subsequently, it has been backed by grants from the FEDER Foundation and the Ministry of Science and Innovation.

Reference article: CRISPR-Cas9 editing of a TNPO3 mutation in a muscle cell model of limb-girdle muscular dystrophy type D2. Javier Poyatos-García, Águeda Blázquez-Bernal, Marta Selva-Giménez, Ariadna Bargiela, Jorge Espinosa-Espinosa, Rafael P. Vázquez-Manrique, Anne Bigot, Ruben Artero, Juan Jesús Vílchez. Molecular Therapy - Nucleic Acids. DOI: https://doi.org/10.1016/j.omtn.2023.01.004