Recognition that the mutations adversely impact regulation of RNA could lead to targeted therapy to correct the problem. The mutation’s location in the prion-like domain might also prove significant. Although the mutations in hnRNPA2B1 or hnRNPA1 appear to be rare, hundreds of other RNA-binding proteins have prion-like domains. Taylor said patients with unexplained neurodegenerative diseases may have mutations in these proteins.
Scientists hope that by creating models of disease in different animals—from flies to reprogrammed human stem cells—research will converge on an answer, or multiple answers. “I think you have to use all these models, with different mutations, in the hopes that there will be one that really does provide the breakthrough,” says Maniatis. For patients and families, that breakthrough can’t come soon enough.