Here, we have demonstrated that M102, a combined activator of NRF2 and HSF1 signalling pathways, has positive therapeutic effects in two different ALS transgenic mouse models and improves motor neuron survival and multiple pathological markers (i.e. oxidative stress, misfolded SOD1, TDP-43 proteinopathy) in a range of human ALS cellular model systems. Here, HSF1 is linked to amyotrophic lateral sclerosis.