Summary:
Primary Ciliary Dyskinesia (PCD) is an untreatable rare disease affecting 1:10000 people. It is caused by mutations in more than 50 different genes and affects organs with motile cilia. Of those, the respiratory system is progressively compromised due to an impaired mucociliary transport.
Current PCD treatments are very limited and only symptomatic. Therefore, there is a high unmet need for therapies that target PCD’s underlying causes.
Ethris has paved a new path from genes to therapeutic proteins using its proprietary, non-immunogenic messenger RNA and LNP technology platforms to discover, design and develop innovative PCD therapies. CCDC40, the lead therapeutic PCD target encoded by ETH42, plays a pivotal role in assembly and function of the dynein regulatory complex, a structure of motile cilia that regulates movement. Patients with CCDC40 mutations are more severely affected by disease compared to carriers of homozygous mutations in other PCD-causing genes.
Zebrafish is considered a good model to mimic human genetic diseases. Around 70 % of the human genes have at least a homologous gene within the zebrafish genome. The transparency of the embryo and larvae allows live imaging assessment of many organs and organelles including cilia.
In the laboratory of Susana Lopes, a CRISPR-Cas9 ccdc40 mutant line was generated and characterized. Animals carrying mutant ccdc40 are characterized by immotile cilia and a curly tail phenotype, making it an ideal model to study therapeutic effects of ETH42.
This project aims at characterizing the therapeutic utility of ETH42 and to develop and characterize novel zebrafish models of PCD.
Funding Institution:
Ethris
Partners:
Ethris
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