MAPT mRNA (RNAi/ASO)

Class

Tau (MAPT)-lowering RNAi/antisense oligonucleotide

MAPT is the gene encoding tau, a protein normally found in neurons where it binds and stabilizes microtubules, the internal scaffolding that supports axonal shape and enables transport of cargo along nerve cells. In a group of neurodegenerative diseases known as tauopathies, which include Alzheimer's disease and several frontotemporal dementias, tau becomes abnormally modified and detaches from microtubules, then misfolds and aggregates into insoluble filaments. These aggregates are thought to spread from neuron to neuron and to correlate closely with regional neuronal loss and cognitive decline, making tau a central therapeutic target. Rather than trying to clear existing aggregates directly, RNA interference (RNAi) and antisense oligonucleotide (ASO) approaches work upstream, at the level of gene expression: they bind the MAPT messenger RNA and trigger its degradation or block its translation, reducing production of new tau protein. Because much of the pathological process depends on continuous synthesis of tau available to misfold, lowering total tau supply is proposed to slow the accumulation of toxic species and reduce the substrate available for cell-to-cell spread. This approach is being explored broadly across tauopathies, where disease severity and progression often track with tau pathology burden rather than with amyloid or other co-existing markers.