Here, we show for the first time that modulating 16% of human disease-altered transcripts only (362 out of 2257 total pathological changes) is sufficient to confer the SRSF1-RNAi dependent neuroprotection previously identified as a promising novel gene therapy approach in C9ORF72-ALS patient-derived neurons and Drosophila [12]. Here, SRSF1 is linked to amyotrophic lateral sclerosis.