UNC13A mis-splicing in ALS/FTD; plus Soteria, Boston Pharma and more

Separate teams published papers in Nature mechanistically linking polymorphisms in UNC13A that increase risk for amyotrophic lateral sclerosis and frontotemporal dementia with TDP-43 pathology thought to drive both conditions. The findings suggest TDP-43 may act, at least in part, via UNC13A, and point to a misplaced exon in UNC13A as a potential new drug target.

One of the groups, led by Michael Ward at NIH and Pietro Fratta at University College London, showed that loss of TDP-43 from the nucleus, an early pathological feature of many cases of ALS and FTD, leads to increased inclusion of a cryptic exon in UNC13A RNA. The cryptic exon causes nonsense-mediated decay and loss of UNC13A protein. ...