Neural transplantation for neurodegenerative diseases: past, present, and future.
After almost 100 years of sporadic, and marginally successful, studies of neural transplantation in animals, we are now on the threshold of a clinical treatment of the damaged brain. The initial studies of neural transplantation have focused on Parkinson's disease, primarily as a model for a more general strategy of "repair by cellular replacement." Parkinson's is known to result from the loss of a small population of cells that produce the essential neuromodulator, dopamine, for much of the brain. Further, the disease is improved significantly, during the early part of its course, by chemical augmentation of dopamine activity through drug therapies, such as L-dopa. Finally, the disease is often fatal in spite of the best medical treatments, therefore justifying more radical therapeutic experiments. If transplantation of brain cells can be accomplished successfully in humans, as it has been in animals, then replacement of a small population of dopamine-producing cells in Parkinson's disease should have important functional effects and possibly reverse the course and symptoms of the disease. Other useful applications will surely follow for conditions affecting millions of people for whom medicine now has only palliative and ineffective treatments. Just as Parkinson's disease is a model clinical condition for testing cellular replacements, fetal neural tissue transplants are also a first step for a broader strategy of molecular and cellular therapies. Fetal cells are, in many respects, the best replacements one could imagine, since precursor cells have the capacity to develop into every cell found in the adult. So, the best replacement for a dopamine neuron would likely be a precursor dopamine neuron or "neuroblast." Animal research through 1985 had demonstrated the unique properties of such fetal cells, but survivability after transplantation had not been attained with primate or human neural tissue. Our programs developed techniques to transplant monkey fetal neural tissue, to cryopreserve it, and to reverse functional effects of the neurotoxin, MPTP, in monkeys. This technique was applied to the collection and preservation of human tissue, and preliminary successful results have been obtained in patients with idiopathic Parkinson's disease. Others have reported success with different techniques in two MPTP-Parkinsonian patients and a small number of patients with idiopathic disease. If the most dramatic improvements can be replicated consistently and the benefits last for a reasonable period without complications, a clinical treatment might develop using "random-source" fetal cadaver cells.
Redmond
D E
DE
Neural Transplant Program, Yale University School of Medicine, New Haven, Connecticut 06510.
Roth
R H
RH
Spencer
D D
DD
Naftolin
F
F
Leranth
C
C
Robbins
R J
RJ
Marek
K L
KL
Elsworth
J D
JD
Taylor
J R
JR
Sass
K J
KJ
D000818:Animals; D016380:Brain Tissue Transplantation; D016332:Fetal Tissue Transplantation; D006801:Humans; D010300:Parkinson Disease / Q000601:surgery*; D010302:Parkinson Disease, Secondary / Q000601:surgery*