More information about project the Zebrafishproject
The aim of the zebrafish project is the testing of the exon-skipping method as a therapeutic application targeting the most frequent mutations leading to USH2A related retinal degeneration and evaluation of its effect in zebrafish.
In today’s society, with its focus on rapid (visual) communication and mobility, Usher patients experience a great decline in quality of life in their professional and personal life. Usher syndrome is a severe genetic disorder, characterized by a loss of hearing and progressive loss of sight. This loss of sight is caused by the deterioration of photosensitive cells (rods and cones) in the retina, often leading to total blindness around the age of 40. However this does leave room for a therapeutic treatment.
Mutations in the USH2A gene are mostly responsible for the occurrence of Usher syndrome in patients (in > 50% of all Usher patients). In at least 10 % of patients with recessive hereditary nonsyndromic retinal degeneration (retinitis pigmentosa), defects in this gene are responsible. It is estimated that over 400.000 people worldwide lose their eyesight because of mutations in the USH2A gene. However, the extremely large size of this gene and the lack of an adequate model system are blocking the view of preservation of sight from patients involved.However, the sheer size of this gene and the lack of an adequate model are obstructing the preservation of sight for patients involved.
So there is an urgent need for:
a) The development of a working method of treatment
b) The development of a suitable model in order to test the effectiveness of this method of treatment
A possible therapeutic approach is the method of exon-skipping, already successfully used in the treatment of Duchenne patients. Here, a small portion of the gene containing the mutation is blocked, so the mutation is skipped, preventing it from dysfunctioning the protein involved.
The USH2A protein will be truncated as a result of the treatment, but it will remain (largely) functional. Whether this remaining function will be sufficient needs to be tested in a model organism.
The animal model in mind for testing the therapeutic effect is the zebrafish. Zebrafish, with the USH2A gene disabled, have problems with hearing and sight. Which makes them a perfect model for people with Usher syndrome type 2A.
Expected results & societal impact:
If successful, this project will lead to a pre-clinical treatment plan for USH2A-related retinal degeneration, aimed at halting the deterioration of sight (within 5 to 10 years).
This will be of enormous influence on quality of life of individual patients. Acquired knowledge can also be transferred and applied to larger groups of patients with other forms of hereditary deafblindness. Therefore this project will have a significant social-economic impact around the world.
Your support for the zebrafish project is very welcome and every donation contributes! Become a frequent donator or make a single donation.
If you have questions about the zebrafishproject, please read our FAQ about the Zebrafishproject.