Neutralizing peripheral circulating IL1 slows the progression of ALS in a lentivirus-infected OPTN^E478G mouse model

Background: Amyotrophic lateral sclerosis (ALS) is irreversible and fatal within 3-5 years, with limited options for treatment. It is imperative to develop a symptom-based treatment that may increase the survival of ALS patients and improve their quality of life. Inflammation status, especially elevated interleukin 1 beta (IL1 beta), has been reported to play a critical role in ALS progression. Our study determined that neutralizing circulating IL1 beta slows down the progression of ALS in an ALS mouse model. Methods: The ALS mouse model was developed by microinjection of lentivirus-carrying OPTNE478G (optineurin, a mutation from ALS patients) into the intra-motor cortex of mice. Peripheral circulating IL1 beta was neutralized by injecting anti-IL1 beta antibody into the tail vein. Enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) were carried out to determine the protein and gene expression levels of IL1 beta. TUNEL assay was used to assess the neural cell death. Immunofluorescent staining of MAP2 and CASP3 was accomplished to evaluate neuronal cell apoptosis. Glial fibrillary acidic protein staining was performed to analyze the number of astrocytes. Rotarod test, grip strength test, balance beam test, and footprint test were conducted to assess the locomotive function after anti-IL1 beta treatment. Results: The model revealed that neuroinflammation contributes to ALS progression. ALS mice exhibited elevated neuroinflammation and IL1 beta secretion. After anti-IL1 beta treatment, ALS mice revealed decreased neural cell death and astrogliosis and gained improved muscle strength and motor ability. Conclusions: Blocking IL1 beta is a promising strategy to slow down the progression of ALS.