Chunk #13 — Therapeutic approaches to toxic tau gain of function — Approach 1: reduce tau gene expression (gene therapy) — Anti-sense Oligonucleotides (ASOs)
Published data from a clinical trial for Huntington’s disease using RG6042, an ASO developed by Roche and Ionis to reduce mutant huntingtin, showed up to 60% lowering of mutant HTT in cerebral spinal fluid. There was 55% to 85% reduction in the cortex, but 20% to 50% in the caudate, and deeper brain regions. Depending on the distribution of ASOs in the brain they may be more efficient in tauopathies with a cortical involvement as opposed to caudate, putamen and thalamic nuclei such as in PSP. The upcoming Phase 3 trial of RG6042 will test whether lowering the levels of a mutant form of huntingtin (mHTT) translates into clinical improvement. [39]
