Prasinezumab Sustained Effect - Nature Medicine
Pagano et al./Nature/2024
Why It Matters
This caught my attention because it's one of the first hints that targeting the underlying protein pathology in Parkinson's might actually slow disease progression long-term, not just treat symptoms. The delayed-start group (who started treatment later) showed less benefit than the early-start group, suggesting timing matters — if this holds up, it would mean earlier intervention is better. But important context: they compared to an external observational cohort, not the original placebo group, which is methodologically weaker and why they call this 'exploratory.'
Key Findings
- After 4 years, early-start participants (who got prasinezumab from day 1) showed 65% slower decline in motor scores OFF medication and 118% slower decline ON medication versus external comparators
- Delayed-start participants (who got placebo first, then prasinezumab) showed less benefit: 51% slower decline OFF medication and 94% ON medication — suggesting early treatment may provide advantages that can't be fully recovered later
- Daily living activities (MDS-UPDRS Part II) also declined 40-48% slower in prasinezumab groups compared to the external comparator cohort
- The study used an external control group from PPMI observational study (303 participants) rather than continuing the original placebo arm, which limits the strength of conclusions
- This was an open-label extension where everyone knew they were getting the drug, and the comparison was exploratory — the authors explicitly state this requires confirmation in future studies