C3 funds development of new LGMD2A/R1 disease model for preclinical testing

Coalition to Cure Calpain 3 (C3) is pleased to announce the funding of a new research award to Dr. Pia Elustondo of AGADA Biosciences. This project will characterize a novel LGMD2A/R1 disease model and utilize this model to test several candidate drugs.

Preclinical drug screening is one of the critical initial steps to develop new treatments for rare diseases such as LGMD2A/R1. Several mouse models have been developed to-date, and researchers have used these to learn more about the disease and test potential therapeutic candidates. However, the mouse models do not show muscle symptoms until they are older, and their symptoms are very mild. Further, mice are relatively expensive to maintain and slow to reproduce. This makes it difficult for researchers to use mice for drug testing.

Dr. Elustondo’s research project proposes to use zebrafish as an animal model to test and find new candidate drugs that will potentially improve LGMD2A/R1 disease symptoms. The investigators have generated three unique zebrafish lines that have disrupted Calpain 3. They plan to characterize these lines to determine if they have a muscle phenotype, and to use them to screen drugs that have the potential to treat this disease.

“Zebrafish are an excellent animal model to study inherited disorders: they mature and reproduce rapidly, are inexpensive to maintain, and their genetics are well-understood. They are even permeable to small molecule drugs!” says C3 Scientific Director Dr. Jennifer Levy. “The development of a zebrafish model of LGMD2A/R1 will allow researchers to quickly and easily test compounds that could be beneficial to patients.”

“We are excited to have the opportunity to work with C3”, says Dr. Elustondo. AGADA provides mouse preclinical efficacy trial services to the international neuromuscular research and pharmaceutical community and plans to transfer this expertise to the zebrafish LGMD2A/R1 model.

“The zebrafish is a versatile model that may help provide key drug candidates for clinical trials in LGMD2A/R1,” says Dr. Anna Cordeiro Santanach, project lead at AGADA. “Zebrafish are very well known as pets, myself I had some growing up, but I didn’t even imagine that would be such interesting and useful model animals for biomedical research! Genome editing technology has empowered us to generate excellent models to do research in a wide range of diseases, especially in genetic disorders as LGMD2A/R1.”