LSP-GR1 is a novel SMO that potently and selectively reduces the expression of the "GluA1-flip" isoform in all cells of the central nervous system (CNS) including neurons (e.g., motor neurons) and white matter cells (e.g., astrocytes) after direct delivery in CSF. Reduced levels of GluA1-flip directly reduce the level of certain AMPA receptors that are associated with excitotoxicity of cells and which are upregulated in epilepsy and ALS patients. LSP-GR1 delays motor deficits, disease progression, and increases lifespan in an ALS mouse model and has been found to decrease seizures and has antiepileptogenic properties in a mouse model of epilepsy.
LSP-GR3 is a novel and selective SMO that directs splicing to reduce expression of the alternatively spliced "GluA3-flip" in motor neurons and surrounding cells. The resulting splice modulation by LSP-GR3, specifically the reduction of the GluA3-flip protein isoform in the CNS, has demonstrated extended longevity in an ALS mouse model.