Fishing for new targets to treat rare metabolic disorders

MetaFish is a collaborative project between the Hubrecht Institute and Scenic Biotech to develop new therapies for children with a rare metabolic disorder for which no treatment is available. 

Inherited metabolic disorders are chronic and often lead to disabilities preventing the patient to engage in socio-economic activities. When looked at individually, inherited metabolic disorders are rare, but combined they have an estimated occurrence of 1 in every 500 newborns, making them one of the main causes of child death. Unfortunately, there are only very few inherited metabolic disorders for which an effective treatment exists. There is therefore a compelling need for the development of new therapies and the identification of therapeutic targets. 

The aim of this project is to develop new zebrafish models for rare metabolic disorders that affect lipid metabolism and lead to heart failure and to use these models to better understand disease progression and to identify modifier genes that can be leveraged as therapeutic targets. To achieve this DNA mutations that have been identified in patients will be built into the DNA of zebrafish. After this, the eggs of these zebrafish will be studied to identify important mechanisms that are responsible for disease progression. Finally, modifiers and small molecules identified by Scenic will be validated for their potential to halt disease progression.  

Eventually, this work may lead to the identification and validation of potential new targets for drug development to treat inherited metabolic diseases in the near future.