Metabolic Therapy for Mitochondrial DNA Maintenance Disorders

Ramon Martí.

Fundació Hospital Universitari Vall d’Hebron - Institut de Recerca (VHIR), Spain.

Mitochondrial DNA maintenance disorders, also known as mitochondrial DNA depletion/deletions syndromes (MDDS), are rare, potentially life-threatening conditions, often affecting infants, that alter the quantity and quality of mitochondrial DNA. No treatment currently exists for most MDDS. This project aims to test an innovative biochemical therapy for MDDS.

The European Union recently approved a treatment for TK2 deficiency using pyrimidine deoxynucleosides, small precursors of mitochondrial DNA replication, to restore deoxynucleotide pools. But because of the properties of purines, extending this approach to other MDDS that might benefit from it is difficult. This project will instead explore an alternative strategy to increase purine deoxynucleoside triphosphates, molecules needed for mitochondrial DNA replication.

This project could have an enormous social impact, as it may offer treatment options for patients who currently have none. This would improve health, autonomy and quality of life while reducing the need for hospital or home care and the associated social and economic burden. The approach may also support broader newborn screening and future therapies for other rare diseases affecting the same metabolic network.

• Marçal Pastor Anglada, Universitat de Barcelona, Spain.

STAGE 1