CHARLIE - CHAnging Rare disorders of LysInE metabolism - LCSB

Synergising the expertise of patient representatives, basic and clinical scientists, to collaboratively develop and validate new therapies and biomarkers.

The project at a glance

Start date:

01 May 2021
Duration in months:

36
Funding:

European Joint Programme Rare Diseases (EJP RD) / Luxembourg National Research Fund (FNR)
Principal Investigator(s):

Carole Linster

Maria Lorena Cordero Maldonado

Clara van Karnebeek (external)

Cristina Fillat (external)

Blair R. Leavitt (external)

About

Rare inborn errors of lysine metabolism such as pyridoxine-dependent epilepsy (PDE) and glutaric aciduria type 1 (GA1) cause debilitating, often progressive neurologic symptoms with chronic care dependency. Medical needs are unmet as current dietary therapy is burdensome and often ineffective, with negative impact on quality of life and socio-economics. Our international CHARLIE project synergises the expertise of patient representatives, basic and clinical scientists, to collaboratively develop and validate new therapies and biomarkers.

We pursue different strategies to avoid brain damage: inhibition of the enzyme upstream to GA1 and PDE with the potential to prevent build-up of highly reactive metabolites as well as gene therapy to replace the missing GA1 enzyme. We will first apply these in PDE and GA1 model systems, such as neuronal stem cells, mouse and zebrafish models. To evaluate and compare the efficacy of these different treatment approaches, we will perform biochemical, morphological, neurobehavioural analyses. We will develop tools for monitoring therapeutic effect, enabling personalized medicine. With our patient advocacy organizations, we will prioritise the most promising treatment strategy/-ies and enhance trial readiness. To inform families, professionals, and stakeholders, we will organise regular meetings and create digital platforms. For successful exploitation we engage industry and policymakers. Together our CHARLIE consortium will translate knowledge from bench to bedside, with drug access for improved outcomes for PDE and GA1 patients and families.