Janus kinase inhibitors are potential therapeutics for amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a poorly treated multifactorial neurodegenerative disease associated with multiple cell types and subcellular organelles. As with other multifactorial diseases, it is likely that drugs will need to target multiple disease processes and cell types to be effective. We review here the role of Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) signalling in ALS, confirm the association of this signalling with fundamental ALS disease processes using the BenevolentAI Knowledge Graph, and demonstrate that inhibitors of this pathway could reduce the ALS pathophysiology in neurons, glia, muscle fibres, and blood cells. Specifically, we suggest that inhibition of the JAK enzymes by approved inhibitors known as Jakinibs could reduce STAT3 activation and modify the progress of this disease. Analysis of the Jakinibs highlights baricitinib as a suitable candidate due to its ability to penetrate the central nervous system and exert beneficial effects on the immune system. Therefore, we recommend that this drug be tested in appropriately designed clinical trials for ALS.

Copper release by MOF-74(Cu): a novel pharmacological alternative to diseases with deficiency of a vital oligoelement

“…As with other multifactorial diseases, medications will likely need to target multiple disease processes. 3 On the other hand, Menkes disease is a lethal, neurodegenerative, sex-linked hereditary childhood disease. This is considered an orphan disease.…”