Figure 4 - Simulated fraction of neurons that do not experience an aggregate nucleation event as a function of concentration (10, 30, 100 or 300 nM) and age for httex1Q47, based on Model 1a or 2, and assuming neurons of volume equivalent to cultured ST14A cells.

The dashed lines bracket the age range 31–35 years, the expected age of onset for Huntington disease in individuals with Q47 expansion³⁸.The therapeutic implications of downregulating htt or otherwise sequestering mhttex1 into a conformation resistant to misfolding are demonstrated by simulating a range of concentrations. The probability of aggregate formation is clearly a strong function of mhttex1 concentration, and so therapeutic interventions that only modestly lower mhttex1 might substantially extend the time until a meaningful number of aggregation events occur.