A new primate study offers tantalizing evidence of the potential for embryonic stem (ES) cells to combat the symptoms of a devastating neurological disease.

Parkinson's disease (PD) patients undergo loss of dopaminergic (DA) neurons within the substantia nigra, a brain region that regulates motor function. This neuronal death and drop in dopamine levels lead to disease progression, with patients finding body movements ever harder to control as neurodegeneration proceeds. Pharmacological treatments offer some relief but are of limited efficacy for long-term therapy.

Fetal brain tissue transplants have shown some therapeutic promise, but the extent of recovery seen with this treatment is limited, and the legal and ethical issues associated with such approaches have discouraged further investigation. Studies in mice have suggested that by stimulating the differentiation of ES cells into neurons, a suitable transplant substrate can be produced. Now, a group of Japanese investigators takes this new strategy a step further, presenting an ES cell–based treatment that seems to relieve PD symptoms in cynomolgus monkeys (J. Clin. Invest., January).

ES cells cultured atop a layer of stromal cells tend to differentiate along a neuronal pathway; Kyoto University investigator Yasushi Takagi and his colleagues took this system a step further and found that by detaching their cells from this feeder layer and culturing them in the presence of specific growth factors, they could produce floating 'neurospheres' consisting of incompletely differentiated neural progenitor cells. Takagi's group was able to refine their culture technique further, so that roughly 20% of these cells became DA neurons.

Monkeys treated with a neurotoxin called MPTP develop symptoms closely resembling those observed in PD. The researchers grafted cells from their neurospheres into the brains of symptomatic MPTP-treated monkeys and found significant improvements in their posture and movement relative to sham-operated control animals, improvements that were still apparent up to 10 weeks following transplant. In addition, the animals showed no signs of dyskinesia, a movement disorder that is a common side effect of pharmacological treatment. Histological examination demonstrated that ES-derived cells had repopulated the graft site, resulting in considerably more DA neurons than were detectable in controls.

In an accompanying commentary for the article, Parkinson's Institute (Sunnyvale, CA) researcher J. William Langston describes this work as an important 'milestone': “These investigators have prepared what appear to be authentic DA neurons and used those to reverse parkinsonism in a primate model ... [that] has been proven highly predictive of new symptomatic approaches in the treatment of Parkinson's disease.” He and the authors caution that much work remains; the long-term impact of this treatment, including risk of tumor formation, has not been assessed, and the extent of DA neuron repopulation may not be sufficient to fully retard the progression of PD. Nonetheless, Langston concludes that this work “will advance research aimed at validating the use of stem cells to treat neurodegenerative disease.”