9E4 antibody in mice (paper retracted 2024)

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Eliezer Masliah (corresponding author), Edward Rockenstein and colleagues at the University of California, San Diego, with seven scientists from Elan Pharmaceuticals (Peter Seubert, Dora Games and Dale Schenk among them). Funding: US National Institutes of Health grants (AG 11385, AG 18840, AG 022074, NS 044233) and Elan. PLoS ONE 6(4):e19338, 29 April 2011.

What happened

Lewy pathology appears to pass between cells (landmark 8), so an antibody that catches synuclein outside cells might slow it. The team gave the 9E4 antibody (a mouse antibody aimed at residues 118–126 at the C-terminal end of the protein) by passive immunisation, meaning ready-made antibody rather than a vaccine. Mice of "line D", which overproduce human synuclein like the models in landmark 31, got 10 mg/kg into the abdomen weekly for 6 months (20 per group; control antibody 27-1). The authors reported better water-maze performance, less calpain-cleaved synuclein in axons and synapses, and more clearance through the lysosome.

Retraction. On 13 November 2024 PLoS ONE retracted the paper. The editors cited similar lanes in several western blot panels (Figs 3, 5, 9, S2), irregularities suggesting spliced images, and repeated actin panels across Fig 5, and said the authors did not supply uncropped high-resolution images. Masliah disagreed with the retraction; the corresponding author's reply said the actin panels came from re-probed blots. This is separate from the two papers named in the NIH misconduct finding of September 2024, which NIH did not identify.

Why it moved us toward a cure

9E4 is the mouse antibody that was humanised into prasinezumab (Prothena/Roche), the drug in landmark 63; the first-in-human report says so directly. A later mouse paper from Prothena, with Masliah as a co-author, reports similar effects, so it is not independent of him.

Outcome

Dead end as evidence. The 2011 paper was retracted in November 2024, and no independent study has replicated its mouse result, so it is marked a dead end, as the retracted STING paper is (landmark 54). The lineage is still real: the antibody became prasinezumab, which Roche took into Phase 3 in June 2025 on its human data (landmark 63). The retraction weakens the preclinical case for that drug, not the human trial results.

Sources

• Masliah et al., PLoS One 2011, DOI 10.1371/journal.pone.0019338, PMID 21559417 (page carries the retraction banner)
• Retraction notice, PLoS ONE 19(11):e0313936, 13 Nov 2024, DOI 10.1371/journal.pone.0313936 · Alzforum paper page marked retracted
• Schenk et al., first-in-human PRX002, Mov Disord 2017 (9E4 lineage)
• Games et al., J Neurosci 2014;34:9441–9454, DOI 10.1523/JNEUROSCI.5314-13.2014 (Prothena affiliation; Masliah co-author)
• Roche, 16 Jun 2025: prasinezumab to Phase 3
• Alzforum, "Data fabrication ousted NIA neuroscience director Eliezer Masliah"
• Not yet verified: effect sizes in the retracted paper; whether the Games 2014 data have been independently reproduced.