Transcriptome-based deep learning analysis identifies drug candidates targeting protein synthesis and autophagy for the treatment of muscle wasting disorder

Sarcopenia, the progressive decline in skeletal muscle mass and function, is observed in various conditions, including cancer and aging. The complex molecular biology of sarcopenia has posed challenges for the development of FDA-approved medications, which have mainly focused on dietary supplementation. Targeting a single gene may not be sufficient to address the broad range of processes involved in muscle loss. This study analyzed the gene expression signatures associated with cancer formation and 5-FU chemotherapy-induced muscle wasting. Our findings suggest that dimenhydrinate, a combination of 8-chlorotheophylline and diphenhydramine, is a potential therapeutic for sarcopenia. In vitro experiments demonstrated that dimenhydrinate promotes muscle progenitor cell proliferation through the phosphorylation of Nrf2 by 8-chlorotheophylline and promotes myotube formation through diphenhydramine-induced autophagy. Furthermore, in various in vivo sarcopenia models, dimenhydrinate induced rapid muscle tissue regeneration. It improved muscle regeneration in animals with Duchenne muscular dystrophy (DMD) and facilitated muscle and fat recovery in animals with chemotherapy-induced sarcopenia. As an FDA-approved drug, dimenhydrinate could be applied for sarcopenia treatment after a relatively short development period, providing hope for individuals suffering from this debilitating condition. Scientists used artificial intelligence to find a possible cure for sarcopenia, a disease marked by muscle loss and decreased function. The group, headed by Dr. Jin Woo Choi, used AI to study gene expression patterns in muscle tissues from healthy people and sarcopenia patients. They found a medicine named dimenhydrinate (DH) as a possible cure. The group then experimented with DH on lab-grown muscle cells and mice, discovering that it encouraged muscle cell growth and repair. The scientists concluded that DH could be a hopeful cure for sarcopenia. However, more studies are required to validate these results and to comprehend how DH functions at a molecular level.This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.