Vall d'Hebron Talks by VHIR 'Efficacy and genetic safety of deoxyribonucleosides as a therapy for mitochondrial DNA maintenance disorders'

Speaker: Javier Francisco Ramon Pasías, Postdoctoral researcher Neuromuscular and Mitochondrial Pathology, Vall Hebron Institut de Recerca (VHIR)

Dr. Javier Ramón received his degree in Biomedical sciences in 2015 from the Universitat de Lleida. On his degree he studied the role of the human protein hSPCA1 in calcium and manganese homeostasis using S.cerevisiae as a model. Later, he obtained a master in Advanced microbiology from Universitat de Barcelona and he studied the molecular epidemiology of the human circulating coronaviruses in Hospital Universitari Vall d’Hebron. Then, he stayed in CABIMER (Seville) studying the role of some proteins in double strand break repair through DNA end resection. Finally, in 2018, he incorporated in neuromuscular and mitochondrial pathology lab in Institut de Recerca Vall d’Hebron where he obtained his PhD in 2024 and where he is currently working on treatment of mitochondrial DNA depletion and multiple deletion syndromes using deoxyribonucleosides.

Mitochondrial DNA (mtDNA) depletion and deletions syndromes (MDDS) are diseases characterized by incorrect maintenance of mtDNA resulting in quantitative (depletion) and/or qualitative (multiple deletions and point mutations) alterations of mtDNA. They are rare diseases with heterogeneous clinical presentations (often severe) with no treatment.
Deoxyribonucleoside (dN) supplementation was proposed as a treatment for a type of MDDS, the myopathy due to thymidine kinase 2 deficiency (TK2d). This approach showed efficacy in murine models of the disease, in a cohort of patients treated under compassionate basis, and is currently under clinical trial. Subsequently, in vitro studies have shown that dNs also stimulate mtDNA replication in cells with mutations in other MDDS-associated genes possibly by expanding deoxyrinonucleoside triphosphate (dNTP) concentrations and therefore stimulating the mitochondrial replisome. These results suggest that the same therapy approach could be extended to other MDDS forms.

Host: Dr. Ramón Martí Seves, Head of group Neuromuscular and Mitochondrial Pathology, Vall Hebron Institut de Recerca (VHIR)

Online attendance: https://gencat.zoom.us/j/81216982265