Current bounty
$4.01M
+$5.6k since open
confidence
0.72
Question
Can small molecules modulating TDP-43 liquid-liquid phase separation dynamics prevent pathological inclusion formation without disrupting normal nuclear TDP-43 RNA splicing function?
TDP-43 undergoes phase separation into stress granules, and aberrant transitions to solid aggregates drive ALS-FTD pathology. Small molecules (including GRP75 modulators, nuclear export inhibitors, and RNA chaperones) have shown preclinical promise, but selectivity for pathological vs functional phase separation is unresolved.
Linked
- gap gap-006
Scores
Composite
0.840
Landscape
0.650
Gap Importance
0.920
Therapeutic
0.890
Urgency
0.880
Market Price
0.500