Neurturin autopsies (Bartus)

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

Raymond Bartus and colleagues at Ceregene (Bartus, Herzog, Wilson, Brown and Siffert were employees; Johnson, Olanow, Mufson and Kordower were consultants paid in cash and stock options) and collaborating centres. Movement Disorders, 2011;26:27–36 (online Nov 2010). A Michael J. Fox Foundation grant to Bartus helped defray costs of the clinical trial.

What happened

CERE-120 delivered the neurturin gene into the putamen. The idea was that neurturin would travel back along the nerve fibres to the cell bodies in the substantia nigra. See landmark 147.

• Method. Immunostaining of brains from two patients who died after treatment (a 59-year-old on day 90 of a pulmonary embolism; a 73-year-old on day 47 of a heart attack; three hemispheres in all), compared with 10 to 11 treated rhesus monkeys (young, aged and MPTP-parkinsonian).
• Result. Neurturin was present in the putamen in every patient (about 15% of putamen volume). In the nigra cell bodies there was only rare neurturin in patients, but plenty in all monkeys. Signs of neurturin activity were sparse in patients, and clear in monkeys.
• Authors' view. The nerve fibres in advanced Parkinson's probably transport poorly, so the drug stays at the nerve endings. They proposed treating both the putamen and the nigra.

Why it moved us toward a cure

It offered an explanation for the failure of landmark 147 as a delivery problem, not necessarily a growth-factor problem. The nigra-plus-putamen trial in landmark 147 had already started (registry start Oct 2009), so this paper supported that design rather than leading to it. The authors said future trophic-factor work must reach both the nerve endings and the cell bodies.

Outcome

Advanced. Two patients is a very small sample, and these were treated only in the putamen, early after surgery (days 47 and 90). Later autopsies by the same group (Chu et al., Brain 2020; two patients 8 and 10 years after treatment) found neurturin in about 10 to 19% of remaining nigral neurons after putamen-only treatment and 22 to 39% after putamen plus nigra treatment, with no clinical benefit, so nigral reach was limited but not absent. A 2023 follow-up (Mov Disord) of two patients at 10 years reported similar limited expression. No correction or retraction was found. Whether later growth-factor trials explicitly built in this lesson is not shown in the sources read.

Sources

• Bartus et al., Mov Disord 2011, DOI 10.1002/mds.23442 (PMID 21322017)
• Chu et al., Brain 2020;143:960–975, DOI 10.1093/brain/awaa020 (PMC7089653) · Chu and Kordower, Mov Disord 2023;38:1728–1736, DOI 10.1002/mds.29518
• Not yet verified: whether the 2023 Mov Disord paper studies the same two patients as the 2020 Brain paper (both report two patients at about 10 years); PubPeer not checked.