iPSC-derived neurons work in monkeys

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

Tetsuhiro Kikuchi, Asuka Morizane, Daisuke Doi, Jun Takahashi and colleagues (16 authors) at CiRA, Kyoto University, with Malin Parmar (Lund). Funding was not stated on the CiRA release and the paper's funding statement was not read.

What happened

The team made dopamine-neuron precursors from human induced pluripotent stem cells (iPSCs), from both healthy donors and Parkinson's patients, and grafted them into cynomolgus monkeys (Macaca fascicularis) made parkinsonian with the toxin MPTP. Spontaneous movement increased after grafting, and CiRA reported improvement over two years. The grafted neurons extended dense fibres into the host striatum whether the cells came from patients or healthy donors. Cells sorted for the floor-plate marker CORIN formed no tumours for at least two years. Donor cell quality, more than cell number, drove how many dopamine neurons survived; the team proposed 11 quality-marker genes, including Dlk1. MRI and PET tracked graft survival and function, and the immune response, without further surgery. Nature 548:592–596, August 2017.

Why it moved us toward a cure

It was the primate proof that human iPSC-derived neurons survive, function and can be monitored, which de-risked the human trial. It also showed cells from Parkinson's patients work, so grafts from a patient's own cells remain an option. It builds on the cell recipe in landmark 17 and uses induced stem cells made by Yamanaka's reprogramming (landmark 32).

Outcome

Advanced. The Kyoto Phase 1/2 trial (Sawamoto et al., Nature 641:971–977, 2025; jRCT2090220384; investigator-initiated, funded by a Japan Agency for Medical Research and Development grant to Takahashi) grafted 7 patients aged 50–69 with donor (allogeneic) iPSC-derived cells and assessed efficacy in 6: no serious adverse events, off-medication motor scores improved in 4 of 6 (mean 9.5 points, 20.4%), and putamen F-DOPA uptake rose 44.7%. Cells for the first three patients were made at Kyoto University and for the later ones at Sumitomo Pharma, whose product is raguneprocel (Amchepry). Sumitomo's product received conditional, time-limited approval in Japan, announced around 6 March 2026 (company release dated by its web address; reported by the Michael J. Fox Foundation on 11 March and Parkinson Canada on 13 March), with seven years to supply confirmatory data. Trial and approval details are in landmark 10. No correction or retraction of the 2017 paper was found; one commentary accompanied it.

Sources

• Kikuchi et al., Nature 2017;548:592–596, DOI 10.1038/nature23664, PMID 28858313 (abstract via Europe PMC; details via the CiRA press release)
• Sawamoto et al., Nature 2025;641:971–977, DOI 10.1038/s41586-025-08700-0 (abstract, cell manufacture and funding from the open full text, PMC12095070)
• Michael J. Fox Foundation on the Japan approval, 11 Mar 2026 · Parkinson Canada, 13 Mar 2026
• Not yet verified: the number of monkeys and cells in the 2017 study; the exact approval date and Sumitomo's own release (not opened).