Intratarget Microdosing for Deep Phenotyping of Multiple Drug Effects in the Live Brain
Frontiers in Bioengineering and Biotechnology March 18, 2022 Jennifer Kim, Sebastian W. Ahn, Kyle Deans et al.
A miniaturized implantable microdevice (IMD) platform, optimized for direct stereotactic insertion into the brain, enables simultaneous measurement of multiple drug effects on native brain tissue in situ. The IMD releases microdoses of single agents or combinations into confined brain regions, allowing spatial analysis of phenotypic, transcriptomic, or metabolomic effects. In murine models of Alzheimer’s disease, microdoses of approved and investigational CNS drugs released from the IMD exhibited in situ phenotypes indicative of therapeutic responses, including neuroprotection, reduction of hyperphosphorylation, immune cell modulation, and anti-inflammatory effects. Local treatments with drugs affecting metabolism regulated metabolite profiles and immune cell function in hMAPT AD mice. The platform should facilitate rapid testing of pharmacological or biological treatment hypotheses directly within native brain tissues.