CDNF AAV Gene Therapy - Nature
Nam et al./Nature/2024
Why It Matters
This caught my attention because CDNF is already in human trials for Parkinson's — this isn't theoretical. The paper shows it might work by calming down two things that go wrong in Parkinson's brains: inflammation and ER stress (when protein-folding machinery breaks). That's valuable mechanistic insight for a drug candidate that's already being tested in people, though we're still looking at mice here.
Key Findings
- AAV gene therapy delivering CDNF reduced motor impairment and partially improved gait problems in MPTP-treated mice (a standard Parkinson's model)
- CDNF treatment reduced levels of inflammatory markers IL-1β and C3 in brain glial cells by measurable amounts
- CDNF decreased expression of ER stress proteins CHOP and GRP78 in astrocytes, suggesting it helps cells manage protein folding problems
- CDNF provided significant protection to the nigrostriatal pathway — the dopamine-producing brain region that degenerates in Parkinson's
- No toxic effects were observed from CDNF expression in the striatum or substantia nigra brain regions