Muscle atrophy is the loss of skeletal muscle mass that leads to muscle weakness and physical disability for patients. It is caused by a range of conditions spanning from rare genetic muscle diseases to common disorders like muscle wasting disease or cachexia.
Muscle atrophy is caused by a change in the balance between protein breakdown and protein synthesis signals. Muscle atrophy can be associated with the activation of pro-inflammatory cytokine pathways which induce protein degradation or inhibit growth factor pathways that promote protein synthesis. Genetic profiling of atrophic muscles has identified a group of ubiquitin ligases (E3 ligases) that are upregulated when muscle atrophy begins. Muscle-specific E3 ligase muscle RING finger protein 1 (MuRF1) has been shown to be upregulated in muscle atrophy. Genetic ablation of MuRF1 in mice has been shown by third parties to render muscles partially resistant to various conditions of muscle atrophy. MuRF1 is a difficult target to address with traditional approaches like small molecules because of the gene family of E3 ligases, however, it may be able to benefit from the specificity of treatment achieved with an siRNA.
Our AOC for muscle atrophy is made up of our mAb targeting TfR1 and an oligonucleotide targeting MuRF1, and is designed to employ both the catabolic and anabolic pathways associated with the degradation of protein in muscle cells.
We are focused on preclinical studies and identifying a muscle atrophy indication best suited for AOCs.