Transcriptomics analysis with various tofacitinib dose treatments of amyotrophic lateral sclerosis mice

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons, with an average lifespan of 2-5 years after diagnosis. Given the lack of effective therapies and growing understanding of the potential role of immunomodulatory drugs in ALS, there is a critical need to expand our knowledge in this area. Here, we assessed the effects of high and low doses of tofacitinib, a Janus kinase (JAK) inhibitor, on disease progression in SOD1G93A mice with prevention (treatment before symptom onset) or via a continuous intervention and cycle treatment (repeating the cycle of one-week treatment and one-week). Low-dose treatment significantly extended mice's lifespan with continuous and cycle regimens. Then, the RNA-seq was performed with the whole spinal cord, and the differentially expressed genes (DEG) were identified between ALS mice and treatment groups. We found that there were strong batch effects among different cohorts. With batch correction, we found 154 DEG between the intervention and ALS group and 95 DEGs between the cycle treatment and ALS group. Among the 95 DEGs, 54 genes were also identified as the DEGs between the ALS and wild-type groups. 32 DEGs showed a reverse direction between cycle treatment vs. ALS and ALS vs. WT groups. Pathways e