Malika Bsibsi began her presentation by providing an overview of Charles River, a contract research organisation (CRO) founded in 1974, which operates in over 100 facilities across more than 20 countries. The company has supported the development of 86% of the novel FDA-approved drugs in 2021. Bsibsi highlighted the company's focus on timelines and currency at every stage of development, offering end-to-end programmes from target discovery to safety in vivo pharmacology.
Bsibsi, based in Leiden, focused on target discovery, using complex cell biology assays with primary and induced pluripotent stem cell (iPSC) lines to validate targets in cell-based assays. She presented data on lead optimisation and in vitro toxicology, aiming to select drugs before in vivo testing and reduce animal use in drug discovery. Bsibsi emphasised the role of microglia in neurodegeneration, particularly in diseases like Alzheimer's, Parkinson's, and ALS. She discussed the activation of microglia, leading to the production of cytokines, chemokines, and nitric oxides, which caused neuronal damage and neurodegeneration.
Charles River developed models for neuroinflammation, using primary cells from the Dutch Brain Bank and partnerships with BiT.bio for neural cell types. Bsibsi detailed the optimisation of assays for microglia activation, including the use of LPS and dexamethasone to study cytokine release. She also discussed the development of assays for the inflammasome pathway, using triggers like BzATP and nigericin to assess IL-1 beta and IL-18 release. Bsibsi highlighted the success of isolating human primary microglia and their functionality in response to various treatments.
In the latter part of her presentation, Bsibsi discussed the development of complex cell models at Charles River, including co-cultures of astrocytes and cortical neurons, and models with oligodendrocytes, microglia, and cortical neurons. These models aimed to predict neurotoxicity and neuroinflammation of hits, selecting drugs before in vivo testing.
