CureMILS - A reprogramming-based strategy for drug repositioning in patients with mitochondrial DNA associated Leigh syndrome - LCSB

The aim of the project is to identify therapeutic strategies for MILS patients.

The project at a glance

Start date:

01 Jun 2021
Duration in months:

36
Funding:

Luxembourg National Research Fund / ERA-Net
Principal Investigator(s):

Antonio del Sol Mesa

About

Mitochondrial DNA (mtDNA)-associated Leigh syndrome (MILS) is a severe early-onset brain disease affecting 1/100,000 newborns. MILS is typically caused by mtDNA mutations in the ATP-generating subunit MT-ATP6. There are no treatments available for MILS. In fact, drug discovery is particularly challenging for MILS. The limited access to patient neural tissue and the difficulty to manipulate mtDNA hinder the development of transgenic animal models and cellular models, which are needed for treatment discovery and development.

In this project we will develop a computational tool to identify chemical compounds targeting desired sets of genes and pathways in a specific cell type. Next, we will apply this tool to build a computational biological model of neural cells affected by the mutation to provide new mechanistic insights into the disease pathology. The computational biological model will be built and validated with diverse omics obtained, in collaboration with Prof. Alessandro Prigione at the Heinrich Heine University and other members of the consortium, from neural cells generated from MILS patients via cellular reprogramming. This model will lead to identify drugs suited for repositioning as interventions in MILS, laying the foundation for a multi-national clinical trial and a concrete path towards a cure for MILS. Moreover, we will establish a paradigmatic working pipeline for reprogramming-driven drug discovery and repositioning for rare neurological disorders.
This is a collaborative project funded by the E-Rare ERA-Net.

Organisation and Partners

Computational Biology
Luxembourg Centre for Systems Biomedicine (LCSB)
Heinrich Heine University (DE)
Fraunhofer IME (DE)
Innsbruck University (AT)
Radboud University Medical Center (NL)
Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences (PL)
Verona University (IT)
University of Helsinki – Finland (FI)