Novel IL-38 Analogues are Potent Inhibitors of Neuroinflammatory Mediators

Description:

SUMMARY

A Tufts University investigator and their collaborators at R&D Systems Inc., have developed novel IL-38 analogues to treat neuroinflammatory and neurodegenerative diseases like Autism Spectrum Disorder (ASD). The novel analogues have demonstrated the ability to be potent inhibitors of proinflammatory mediators secreted from human adult and embryonic microglia.

PROBLEM

ASD is a developmental disorder that is characterized by impaired social interaction and communication. ASD occurs in 1 of 54 children in the USA, but this incidence is predicted to increase to 1 in 40 by 2025. Currently, there are no medications on the market designed to treat the core of ASD symptoms. Instead patients use a broad spectrum of multidisciplinary interventions to manage symptomology. Therefore, there is a increasing unmet need to treat the underlying pathology of ASD.

SOLUTION

The pathogenesis of ASD is unknown but is hypothesized to stem from inflammation in the amygdala, the portion of the brain that regulates behaviors. One pathway of inflammation starts with the activation of microglia within the amygdala through a protein called Neurotensin (NT). Evidence supports that children with ASD have an increased serum concentration of Neurotensin, a peptide known to stimulate microglia to secrete the proinflammatory mediators. Once active, microglia secrete the proinflammatory mediators IL-1B and CXCL8. Thus, the novel IL-38 analogues are designed to treat the focal inflammatory component of ASD by inhibiting the release of proinflammatory mediators.

SUPPORTING EVIDENCE

Through ELISA assays, it is demonstrated that the pretreatment of human adult microglial cells with the novel IL-38 analogues significantly inhibited Neurotensin (NT) induced secretion of IL-1B and CXCL8 (Fig 1a & b). Further, this data was supported in human embryonic cells, as the analogue pretreatment significantly inhibited the secretion of the proinflammatory chemokine CXCL8 (Fig 1c). To note, IL-1B is not produced in human embryonic microglia.

IP STATUS Provisional patent filed July 2020.