Stem cells to transplantable dopamine neurons

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

Sonja Kriks, Jae-Won Shim, Lorenz Studer, Viviane Tabar and colleagues at Memorial Sloan Kettering and Cornell. Paid for by NIH/NINDS, the Starr Foundation, New York State stem-cell contracts (NYSTEM), the European Commission and private foundations, per the paper's acknowledgments. Bemdaneprocel's later development was sponsored by BlueRock Therapeutics; its Phase 1 paper says the initial work (called MSK-DA01) was supported by NYSTEM and an MSK core grant.

What happened

The team showed that earlier failures came from incomplete cell specification. Using small molecules that activate sonic hedgehog and WNT signalling, they made midbrain floor-plate precursors by day 11 and transplantable dopamine neurons by day 25. In 6-OHDA-lesioned mice and rats, the grafts survived long-term, fully restored amphetamine-induced rotation and improved forelimb use and akinesia tests. In two MPTP-lesioned rhesus monkeys, a pilot showed that batches of 50 million precursors could be made and grafted; the monkey data showed survival, not tested recovery. No neural overgrowth was seen in any of the three species. Nature 480:547–551, 2011.

Why it moved us toward a cure

It made scalable, safe human dopamine neurons possible, the foundation for replacing the lost cells rather than only treating symptoms, and a solution to the problems that ended the fetal-tissue approach (landmark 3).

Outcome

Advanced. Bemdaneprocel (BlueRock/Bayer) uses this floor-plate approach, adapted to clinical manufacturing: the Phase 1 paper (Tabar et al., Nature 2025; 12 patients, no adverse events related to the cell product, higher putamen FDOPA uptake at 18 months) cites Kriks 2011 as its protocol source. The sham-controlled Phase 3 exPDite-2 (NCT06944522; about 102 participants; primary endpoint change in diary ON time without troublesome dyskinesia at week 78) was announced by BlueRock on 22 Sept 2025 as having treated its first patient. Details are in landmark 10. PubMed lists three "comment in" notes for Kriks 2011; no correction or retraction was found.

Sources

• Kriks et al., Nature 2011;480:547–551, DOI 10.1038/nature10648 (free PMC3245796)
• BlueRock Phase III release
• Tabar et al., Nature 2025;641:978–983, DOI 10.1038/s41586-025-08845-y · ClinicalTrials.gov NCT06944522
• UCI Health note on the 2025 Nature paper
• Not yet verified: any licence between MSK and BlueRock (the company release does not mention one); the monkeys' functional outcome (pilot of two animals, survival only); PubPeer not checked.