A unique approach to discovery
MapLight’s innovative discovery platform combines three key technologies that provide us with unique insights into atypical neural circuits. Optogenetics identifies the function of key cell types in the brain. Transcriptomics provides a library of potential therapeutic targets within these cells. STARmap enables us to visualize those targets in neural circuits of intact brain tissue. Together, these tools are driving the development of multiple first-in-class, highly targeted therapies for the most difficult-to-treat brain disorders and symptoms.
Optogenetics is a laboratory technique that enables real-time manipulation of the neural circuits that are responsible for the clinical manifestations of central nervous system disorders.
Optogenetics enables real-time manipulation of the neural circuits responsible for the clinical manifestations of central nervous system disorders. Neural circuits are prioritized for in-depth optogenetic analysis based on existing disease-relevant human functional neuroanatomy (fMRI), human functional neurosurgery (DBS), and rodent optogenetic literature.
Optogenetics allows us to turn neurons “on” or “off” with the flick of a light switch. We start with opsin proteins that can be activated or deactivated with light– excitatory ion channels such as ChR2 that trigger action potential firing, or inhibitory Cl– pumps such as NpHR that silence neural activity. We then use genetically targeted viruses to specify which cells contain the light sensitive opsins, so that only cells in the circuit of interest will be responsive to the light. This process provides highly precise identification and control of the exact circuits and brain cells responsible for triggering pathological disease symptoms.
Circuit function is systematically tested across multiple nodes in a network, and parameters are adjusted to define the full range of symptoms controlled by individual circuits.
A unique approach for identifying the gene expression pattern of each cell type in the brain, enabling the identification of treatment targets within specific brain circuits.
With transcriptomics, gene expression profiling is used to identify gene products capable of modulating different circuit elements and the disease symptoms they mediate. Genes that have high specificity for the circuit of interest are evaluated as potential targets so that drugs can be developed with enhanced efficacy and fewer side effects.
MapLight’s proprietary cell atlas contains gene expression data from millions of single cells across the central and peripheral nervous systems. This rich resource is used to fuel the identification of novel cell types and targets, to rank candidates by specificity to the circuit of interest, and to predict synergistic drug combinations.
A patented technology that identifies transcription patterns across brain circuits in native brain tissue in three dimensions, revealing which circuits may be reached by specific treatments.
With STARmap technology, hundreds of gene transcripts can be assayed in situ, preserving the spatial integrity and anatomical architecture of the intact brain circuit. This allows us to efficiently locate drug target candidates within key neural circuits and combine this information with functional (e.g. immediate early gene expression) and anatomical (e.g. projection pathway) readouts.
The architecture and genetic composition of circuits can be confirmed across species to prioritize targets most likely to effectively translate from preclinical models into clinical patient populations.