Neural transplantation for Parkinson's disease: the challenge

June 19, 2003

Despite continued research and development of drugs for the treatment of neurodegenerative diseases, disorders such as Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis, are poorly treated. However, the degeneration and death of selected populations of neurons in these disorders-eg, dopaminergic neurons of the substantia nigra in PD-makes these diseases amenable to the development of cell-replacement therapies.

In the July issue of The Lancet Neurology, many aspects of cell-replacement therapies are described in a Forum article with contribution from leading investigators from Europe and the USA. The authors discuss the ethics of transplantation for PD, alternative cell sources, and how we should proceed with clinical trials. "Replacement of dopaminergic neurons in patients with Parkinson's disease (PD) has spearheaded the development of this approach and was the first transplantation therapy to be tested in the clinic", say Anders Bjorklund and Steve Dunnett in their introduction to the topic. "In our opinion, transplantation of fetal dopaminergic neurons is based on a solid rationale and open-label trials have provided convincing proof of principle that transplants can work-and work well-in some patients."

Transplantation of fetal tissue for the treatment of Parkinson's disease (PD) is not a new concept; the first animal experiments were done in the late 1970s and the first transplants of human fetal tissue into patients with PD were done in the late 1980s. The results of these small open-label studies showed that grafted fetal tissue can survive and can be therapeutically effective, allowing patients to reduce their dopamine-replacement medication.

On the basis of these initial studies, a randomised controlled trial of transplantation for PD was done in the USA. The results were disappointing; there was no overall improvement, although patients under 60 years of age did show some improvement on a PD rating scale after transplantation. The study also highlighted a worrying side effect of this treatment; severe dyskinesias were reported in 15% of patients who received transplants.

However, researchers remain confident that, with further research into the variables that control clinical response, this approach may become a viable treatment for patients with advanced PD. For other neurodegenerative disease, such as Huntington's disease, the potential may be even greater. In an accompanying review article, Ole Isacson discusses the use of cells as therapeutic agents in neurodegenerative diseases in general. " . . . More research into the generation, selection, and transplantation of cells into the brains of responsive patients and improved understanding of these procedures are essential for the future success of cell-based therapies in neurology", concludes Ole Isacson.

The forum is broken down into six sections:
1. Neural transplants in Parkinson's disease: do they work?
Anders Bjorklund and Stephen B Dunnett
2. How can we make transplants of embryonic neural tissue more effective?
Patrik Brundin and A Jon Stoessl
3. Transplantation of embryonic dopaminergic neurons in PD: the Colorado experience
Curt R Freed and Robert E Breeze
4. Human fetal neural transplants in patients with PD: ethical considerations
Marc Levivier and Marc Peschanski
5. Are stem cells a valid alternative to human fetal tissue?
Lorenz Studer
6. Porcine neural xenografts for the treatment of neurodegenerative diseases
Roger Barker
-end-
Also in this month's issue:
The production and use of cells as therapeutic agents in neurodegenerative diseases
Ole Isacson

Lancet

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