Cell-Permeable Succinate as Treatment for Mitochondrial Disease - in vivo Proof of Concept

Important results from the project

The project, with the aim to develop a novel pharmaceutical treatment for patients with genetic mitochondrial diseases caused by dysfunction of complex I of the mitochondrial respiratory chain, has progressed from TRL3 to TRL4. The potential for disease intervention has expanded from the initial focus on acute intravenous administration to chronic oral administration.

Expected long term effects

A lead candidate, which fulfilled all stop/go criteria set up in WP1-2 of the project plan, has successfully been selected. Selection was based upon demonstration of tolerability in vivo, and delivery of succinate with sequential metabolism in the central nervous system. The development and business plans have been updated and changed to reflect the expanded potential of the pharmaceutical concept following demonstration of feasibility of chronic oral administration.

Approach and implementation

All planned activities were performed successfully, with the exeption of the use of the genetic model Ndufs4. Alternative proof of concept studies have been performed outside of the Swelife-supported project. A registry study has been performed by NeuroVive’s partner, the Children’s Hospital of Philadelphia (www.ncbi.nlm.nih.gov/pubmed/28442181). The treatment opportunities has been discussed with patient advocate organization and treating physicians at workshops and scientific meetings where we have been invited to present (www.ncbi.nlm.nih.gov/pubmed/29074296).