Published Date: 5/14/2025
Value Proposition: Novel antisense oligonucleotide (ASO) directly targeting a microRNA-mediated mechanism responsible for autophagy reduction and neurodegeneration in Huntington’s disease (HD) improving patient outcomes in pre-HD subjects.
Technology Description
Researchers at Washington University in St. Louis have developed an antisense oligonucleotide (ASO) inhibiting a miRNA (miR-29b-3p) as a treatment for Huntington’s disease (HD) by promoting neuronal survival and rescuing neurons from degeneration. MiR-29b-3p is an age-associated miRNA significantly upregulated in post-onset HD medium spiny neurons (MSN). Increasing miR-29b-3p results in significant decreases in autophagy activity and induces neuronal degeneration in pre-HD-MSN.
Figures: Images (left) and quantification (right) of HD-MSNs. Inhibition of miR-29b results in significant reduction of cells with IBs, alleviating neuronal degeneration.
Stage of Research
Researchers have validated this invention using multiple MSNs reprogrammed from patient fibroblasts, showing that miR-29b-3p promotes HD-MSN degeneration by downregulating STAT3, a key regulator of autophagy and cell death. Promisingly, the miR-29b-3p ASO increases/restores STAT3 in HD-MSNs.
Publications
Oh, Y.M., Lee, S.W., Kim, W.K. et al. Age-related Huntington’s disease progression modeled in directly reprogrammed patient-derived striatal neurons highlights impaired autophagy. Nat Neurosci 25, 1420–1433 (2022).
Applications
- Treatment for Huntington’s Disease.
Key Advantages
- Effective rescue of HD-MSN from neuronal degeneration.
- miR-29b-3p/STAT3 interaction is identified to be specific to humans.
Patents
US Non-provisional patent application pending – Application #18/348,263
