Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the loss of motor neurons and skeletal muscle wasting. Although growing evidence points to skeletal muscle as an active player in ALS, its contribution to disease progression and its potential as a therapeutic target remain incompletely understood. We previously showed that inhibiting FOXO1, a transcription factor involved in muscle atrophy and metabolism, has beneficial effects in cellular and Drosophila models of ALS. In this study, we investigated whether pharmacological FOXO1 inhibition could improve disease outcomes in the hSOD1G93A mouse model of ALS. Mice were treated with the FOXO1 inhibitor, starting either before the onset of symptoms or after disease onset. We evaluated motor function, survival, body weight, skeletal muscle pathology and muscle gene expression. Our findings revealed limited benefits of FOXO1 inhibition, highlighting the complexity of skeletal muscle alterations in ALS and the need to explore complementary therapeutic strategies.
Non-small cell lung cancer (NSCLC) often occurs with a well-defined inflammatory tumor microenvironment (TME). Continuous inflammatory conditions in the TME induce cell damage and death, resulting in the release of damage-associated molecular patterns (DAMPs). DAMPs are sensed by toll-like receptors (TLR) and interleukin-1 receptor (IL-1R) families signaling through the adaptor protein MyD88. Many attempts have been made to modulate the effects of the receptors in cancer but being the central hub of these inflammatory cascades, MyD88 modulation may be a more effective strategy. However, the implication of MyD88 in coordinating cancer-intrinsic inflammation and cancer progression remains to be clearly explained. We are convinced that MyD88 may exert divergent effects depending on the oncogenic context, but enhancing tumor progression in highly inflamed tumors. Our objective is to delve deeper into the multifaceted role played by MyD88 in NSCLC, a highly prevalent and deadly disease, to identify the specific contexts in which modulating MyD88 or its effectors may be an effective anti-tumor immunotherapy for the disease.