Valérie Allamand, PhD
Suppression of COL6 premature termination codons by anticodon-edited tRNAs
COL6 mutations that introduce premature stop codons show the most severe clinical presentations. Individuals who are affected by these mutations, about 10% of patients with COL6-RD, typically do not have COL6 synthesized in the extracellular matrix. Dr. Allamand will correct the production of COL6 by using anticodon engineered tRNAs. The findings will provide data for in vivo approaches on treated cells and pre-clinical studies in COL6-RD mouse models with nonsense mutation. Additionally, the technique used in this project can be applied to other neuromuscular diseases caused by nonsense mutations.
“The funded project relies on a collaboration with Dr. Christopher Ahern (University of Iowa, Iowa City, IA) who published in 2019 a very elegant approach to correct premature termination codons (PTC). My group in the Research Center in Myology (Paris, France) focuses on congenital muscular dystrophies (CMD), notably COL6-related diseases (COL6-RD). The grant will allow us to assess the efficacy of Dr. Ahern’s approach in cells (fibroblasts) derived from patients’ skin biopsies. The next step will be to move to a mouse model developed in my group. This research is important to me because I believe that the results obtained can have a significant impact on patients’ lives,” said Dr. Allamand. “I am very grateful to MDA for this Idea Grant Program that will enable us to obtain in vitro proof-of-concept results and hopefully move quickly to pre-clinical studies. Developing therapeutic strategies for patients is our motivation and the grant allows us to move forward with this promising strategy that we plan on developing also for other types of CMDs.”