First fetal dopamine-cell transplants

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

Olle Lindvall, Anders Björklund, Patrik Brundin and colleagues (Lund University), building on the rat grafts in landmark 23.

What happened

Lund grafted fetal midbrain tissue into a patient in November 1987 (Lund MultiPark history). The 1990 Science paper (Lindvall, Brundin, Widner, Rehncrona, Gustavii, Frackowiak, Leenders, Sawle, Rothwell, Marsden) reports one severely affected patient: tissue from fetuses of 8 to 9 weeks' gestation was implanted on one side, into the putamen, by stereotactic surgery. Fluorodopa PET showed restored dopamine synthesis and storage in the grafted area, and rigidity, slowness and "on-off" fluctuations improved, most on the side opposite the graft. These open-label reports (no placebo group) led to the controlled trials that followed:

• Freed et al., 2001, 40 patients: main measure missed (landmark 317).
• Olanow et al., 2003, 34 patients: no significant overall effect (landmark 318).
• TRANSEURO, an open-label European trial of 11 grafted patients, compared with 16 ungrafted patients: no overall clinical effect at 3 years (landmark 319).

Many patients in the later trials developed uncontrolled movements (dyskinesias) caused by the graft (landmark 215).

Why it moved us toward a cure

It proved that replacement neurons can survive and make dopamine in a human brain, and so opened cell therapy. It also showed what cell therapy must solve: a standard cell source, the right dose and patients, and no graft-induced dyskinesias.

Outcome

Superseded by stem-cell-derived neurons (landmark 10).

Sources

• Lindvall et al., "Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease", Science 1990;247:574–577, PMID 2105529 (abstract read via Europe PMC; record)
• Lund MultiPark history
• Not yet verified: other open-label graft series of the 1990s (this file does not cover them); the patient's outcome beyond the 1990 paper; the surgeon and the date of the first operation beyond the Lund history page (which gives November 1987); the full text of the 1990 paper.