Developing clinical mouse models with KLHL40 deficiency
Embargo Date
2026-10-01
OA Version
Citation
Abstract
Nemaline Myopathies greatly impact the life of all patients who endure this disease. The symptoms of nemaline myopathy range greatly depending on the specific gene affected, affecting lives of some more than others. Nemaline Myopathy 8, caused by Klhl40 deficiency is one of the most severe cases of neuromuscular disorders. The clinical human presentation of KLHL40 NM are hypotonia, muscle weakness, feeding difficulties, respiratory issues, and premature death. There is currently no cure for Klhl40 deficiency, but progress in similar neuromuscular disease have been made, allowing for a potential therapy to be modeled off existing ones. To create a therapy, suitable animal models needed to be made to test these therapies on as well to monitor the progression of the disease. To develop therapies for Klhl40 deficiency, we have developed a mouse model that exhibits early skeletal muscle weakness and lethality similar to patients. AAV-KLHL40 treatment of mice resulted in promising preliminary data on improvement in muscle function and life span. Future studies will result in preclinical assessment of the effectiveness and long-term improvement in muscle structure and function in KLHL40-NM.
Description
2024