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from The Harvard Mahoney Neuroscience Institute Letter
Volume 3 Number 1 1994. Copyright The Fellows of Harvard College
FETAL NERVE CELL TRANSPLANTATION:
ADVANCES IN THE TREATMENT OF PARKINSON'S DISEASE
from the Neuroregeneration Laboratory
There are billions
of nerve cells in a human brain. In neurodegenerative disorders,
such as Parkinson's and Huntington's disease, selective loss of
some 500,000 cells in critical brain regions can lead to devastating
symptoms. Nerve cell death in these diseases occurs over years or
decades and results in specific signs and symptoms, such as lack
of movements (in Parkinson's) or excess movements (in Huntington's
disease). Although several theories have been presented for the
causes of neurodegenerative disease, the exact pathological mechanisms
involved are not known.
are few and limited in effect and duration. Neuroscientists and
neurologists working in this field have attempted to replace neurotransmitters
lost in the disease process by pharmacological treatments. L-dopa
or related agents bring relief to many Parkinsonian patients, but
L-dopa becomes ineffective over time and debilitating side-effects
develop with prolonged use. No equivalent drug alternative exists
for patients with Huntington's disease.
therapies for these patients are largely ineffective, alternative
strategies are being developed. Intense research efforts are directed
towards drugs that may block nerve cell death and novel cell-based
therapies, which replace defective nerve cells.
Can we stop or
halt the progression of nerve cell death in neurodegenerative diseases?
Since we do not
know the exact way in which specific nerve cell groups die in the
brains of Parkinson or Huntington patients, it is difficult to devise
successful strategies to treat these slowly developing diseases.
However, we have hints of the general mechanisms involved in the
neuronal cell death.
produced within the body or introduced from outside, may be involved.
In Parkinson's disease it was recently suggested that the initiation
of L-dopa therapy could be delayed for a year or so if the patients
were treated with the inhibitor of the enzyme called Mono-Amine-Oxidase
B (MAO-B) (Deprenyl). The idea for this treatment came from observations
of people who developed a form of Parkinson's disease after illicit
use of a drug called MPTP. MPTP had caused selective degeneration
of a set of neurons in a small region of the mid-brain, neurons--called
Ôdopaminergic'--that produce the neurotransmitter dopamine.
This type of nerve cell death is also seen in most forms of Parkinson's
inhibitors can prevent the formation of toxic compounds from MPTP
in the brain, it was reasoned that, if similar substances were responsible
for injuring nerve cells in the more common forms of Parkinson's
disease, then MAO-B inhibition could be beneficial. Initial, highly
publicized clinical trials suggested that MAO-B inhibitors could
slow down the progression of the disease, but more extensive clinical
trials suggest that these changes are probably due to effects other
than prevention of dopaminergic nerve cell death.
While one can
be hopeful about future treatments to prevent neuro-degenerative
diseases, current drug therapies or neuroprotective methods do not
provide sufficient help to patients. Another rational approach to
treat Parkinson's disease is therefore to replace damaged brain
cells with new functional cells and thereby compensate for the loss
of essential nerve cell groups.
Such cell transplantation
to the brain is a relatively novel therapeutic method (compared
to drugs) and pre-clinical attempts have been made to replace missing
neurotransmitters with cells capable of producing dopamine from
a gland above the kidney, the adrenal medulla, fetal neurons or
genetically engineered cells.
In clinical trials,
the difficulty lies not only in choosing the best cellular replacement
for the lost neurons, but is further complicated by ethical controversies
and profound technical problems associated with potential cell sources
such as human fetal cells or genetically engineered cells.
medulla or genetically engineered cells.
Each cell source
used for transplantation has advantages and disadvantages. A cell
source that initially looked somewhat promising for cell replacement
therapy in Parkinson's disease was adrenal medulla cell implants
(grafts). As the patient's own adrenal medulla could be used, this
transplantation procedure circumvented many donor issues. The therapeutic
idea came from the belief that sufficient amounts of dopamine could
be produced by such intracerebral grafts to compensate for the loss
of this neurotransmitter in Parkinson patients.
The first small
clinical study (4 patients) by an experienced research team showed
only modest improvements in the implanted patients. However, this
was followed by uncontrolled clinical studies outside the U.S.,
claiming that Parkinson patients had been cured by adrenal medulla
grafts. These claims were subsequently determined to be wildly exaggerated,
later clinical trials in the U.S. and elsewhere have failed to show
any systematic or lasting benefit from adrenal medulla grafts and
no evidence exists that such grafts can produce sufficient amounts
of dopamine to overcome the deficit produced by the disease.
circuitry works mainly by nerve cells with fibers contacting other
nerve cells at fine multiple sites called synapses. Synapses provide
conditions of specific communication between nerve cells and also
allow for control of neurotransmitter release and levels. Implantation
of adrenal medulla cells cannot achieve these conditions since synapses
are not created to any significant degree by these cells.
techniques in molecular biology we can insert genes into some types
of cells. These novel methods can be employed to generate cell sources
that release dopamine. Such cells are advantageous compared to adrenal
medulla cells because they can be made to produce large amounts
of dopamine. However, available genetically engineered cells are
non-neuronal and therefore lack the ability to form synapses.
If dopamine producing
neuronal cells are constructed that can give rise to synapses and
function optimally in existing host brain circuitry, such genetically
engineered cells may also become clinically useful. Currently, the
only way to obtain such brain circuitry reconstruction in animal
experiments, and probably in patients, is through the use of fetal
Are aborted human
fetal cells needed for nerve cell transplantation?
experiments over the last decade provide evidence that implanted
fetal neurons can replace dead host neurons, form effective synapses
with host neurons and produce necessary neurotransmitters. In this
way, minute amounts of implanted immature rat, mouse, pig or human
dopamine cells have been shown to grow in rat animal models of Parkinson's
disease and effectively reduce most symptoms. The fetal nerve cells
can be injected into a desired brain location as a liquid containing
cells. The number of implanted dopaminergic cell needed for recovery
of movement represents only about one- tenth of a million of the
total number of nerve cells in the brain.
Over the last
4 years, studies with implantation of human fetal dopaminergic cells
into patients suffering from Parkinson's disease indicate that patients
can improve substantially by this treatment. However, the experience
so far is limited to a few patients, and the pioneering clinical
teams differ markedly in their success and transplantation methods
regarding this method to treat Parkinson's disease is mainly an
ethical debate about abortion of human fetuses. This linkage with
the abortion issue is unfortunate since the use of human cells is
probably not necessary, or even desirable, for applying this transplantation
method to patients.
of a major medical treatment that will rely on the event, or availability,
of aborted human fetal donor tissue is undesirable. Second, the
use of human fetal tissue may be associated with infection risks
to the patients with implants. Third, techniques for coordinating
and handling aborted human fetal brain tissue have proved to be
difficult, and may not be provide a large enough number of surviving
dopamine cells for patients to recover from the disease.
To overcome these
problems, fetal cells from non-human fetuses (such as porcine) or
other biotechnology derived nerve cells can likely be developed
as safe and effective alternative cell sources for transplantation
to patients with neurodegenerative diseases.
is Associate Professor in the Program in Neuroscience at Harvard
Medical School and Massachusetts General Hospital and Director of
the Neuroregeneration Laboratory at McLean
Hospital, Belmont, MA 02178. This article was prepared as an invited
commentary on controverisies in transplantation for Parkinson's
on Transplantation for Parkinson's Disease
- AN 95089583
- AU Kupsch A.
- IN Klinikum
Grosshadern, Neurological Unit, Ludwig-Maximilians-University,
- TI Neural transplantation,
trophic factors and Parkinson's disease. [Review] SO Life Sciences.
- AB Part 1 of
this update on new restorative therapeutic strategies against
Parkinsons's disease focuses on transplantation of dopamine-secreting
tissue. Special emphasis is put on clinical trials with fetal
mesencephalic cells. Problems and potential alternative approaches
are discussed. Part 2 emphasizes progress in the related field
of neurotrophic factors for dopaminergic midbrain neurons. [References:
- AN 95066035
- AU Aminoff MJ.
- IN Department
of Neurology, University of California, San Francisco, School
of Medicine 94143-0114.
- TI Treatment
of Parkinson's disease. [Review]
- SO Western Journal
of Medicine. 161(3):303-8, 1994 Sep.
- AB Pharmacotherapy
with levodopa for Parkinson's disease provides symptomatic benefit,
but fluctuations in (or loss of) response may eventually occur.
Dopamine agonists are also helpful and, when taken with low doses
of levodopa, often provide sustained benefit with fewer side effects;
novel agonists and new methods for their administration are therefore
under study. Other therapeutic strategies are being explored,
including the use of type B monoamine oxidase inhibitors to reduce
the metabolic breakdown of dopamine, catechol-O-methyltransferase
inhibitors to retard the breakdown of levodopa, norepinephrine
precursors to compensate for deficiency of this neurotransmitter,
glutamate antagonists to counteract the effects of the subthalamic
nucleus, and various neurotrophic factors to influence dopaminergic
nigrostriatal cells. Surgical procedures involving pallidotomy
are sometimes helpful. Those involving cerebral transplantation
of adrenal medullary or fetal mesencephalic tissue have yielded
mixed results; benefits may relate to the presence of growth factors
in the transplanted tissue. The transplantation of genetically
engineered cell lines will probably become the optimal transplantation
procedure. The cause of Parkinson's disease may relate to oxidant
stress and the generation of free radicals. It is not clear whether
treatment with selegiline hydrochloride (a type B monoamine oxidase
inhibitor) delays the progression of Parkinson's disease, because
the drug also exerts a mild symptomatic effect. Daily treatment
with vitamin E (a scavenger of free radicals) does not influence
disease progression, perhaps because of limited penetration into
the brain. [References: 57]
- AN 95007800
- AU Koutouzis
TK. Emerich DF. Borlongan CV. Freeman TB. Cahill DW. Sanberg PR.
- IN Department
of Surgery, University of South Florida College of Medicine, Tampa
- TI Cell transplantation
for central nervous system disorders. [Review] SO Critical Reviews
in Neurobiology. 8(3):125-62, 1994.
- AB Initially,
the specific aim of transplantation studies was to investigate
the regenerative capabilities of the mammalian nervous system.
From this underlying impetus, a myriad of knowledge, spanning
from molecular biology to neurobiology, has enhanced our understanding
of regeneration and the applicability of fetal tissue transplantation
in treating various neurodegenerative diseases. Current evidence
suggests that transplantation of fetal neural tissue ameliorates
the neurobiological and behavioral changes observed in animal
models of central nervous system (CNS) disorders. In light of
numerous basic science studies, clinical trials have begun to
evaluate the potential of neural transplantation in treating human
diseases. Indeed, modest progress has been reported in the treatment
of Parkinson's disease. However, whereas fetal tissue transplantation
has reached considerable success, it has also been observed to
produce either no beneficial effects, magnify existing behavioral
abnormalities, or even produce a unique constellation of deficits.
Thus, while the prospects are promising, further investigations
aimed at improving and refining existing transplantation paradigms
are warranted before neural transplantation techniques can be
of widespread value. This review article attempts to provide an
overview of the neuroanatomical, neurochemical, and behavioral
effects produced by transplanted fetal tissue in several animal
models of CNS disorders. We have attempted to present both positive
and adverse effects and to critically analyze the suitability
of neural transplantation as a therapy for the various neurological
disorders. In addition, alternative approaches, including the
use of encapsulated neural tissue implants and genetically engineered
cell lines along with their clinical potential, are discussed
when appropriate. [References: 275]
- AN 93283757
- AU Widner H.
- IN Department
of Neurology, University Hospital, Lund, Sweden. TI Transplantation
and surgical treatment of parkinsonian syndromes. [Review]
- SO Current Opinion
in Neurology & Neurosurgery. 6(3):344-9, 1993 Jun.
- AB Neurosurgical
attempts to correct parkinsonism use strategies aimed either at
alleviating the underlying dopamine deficiency or at correcting
abnormal compensatory effects in neural circuits within the basal
ganglia. During the review period, clinical trials of four different
neurosurgical approaches were reported. These approaches are intracerebral
transplantation of fetal dopamine neurons, intracerebral transplantation
of adrenal medullary tissue, tremor-reducing surgical lesions
in the ventrolateral thalamus, and ventroposterior pallidotomy
aimed at reducing akinesia and rigidity. Experimental studies
in rats and monkeys designed to explore mechanisms of graft actions
were also reported. [References: 33]
- AN 93063066
- AU Widner H.
Tetrud J. Rehncrona S. Snow B. Brundin P. Gustavii B. Bjorklund
A. Lindvall O. Langston JW.
- IN Department
of Neurology, University Hospital, Lund, Sweden. TI Bilateral
fetal mesencephalic grafting in two patients with parkinsonism
induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
- SO New England
Journal of Medicine. 327(22):1556-63, 1992 Nov 26. AB BACKGROUND.
Intracerebral transplantation of fetal dopaminergic neurons is
a promising new approach for the treatment of Parkinson's disease.
Patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP) have a relatively stable lesion limited to the nigrostriatal
system, rendering them ideal candidates for transplantation. Improvement
of motor function after neural grafting has previously been observed
in nonhuman primates with MPTP-induced parkinsonism. METHODS.
We grafted human fetal tissue from the ventral mesencephalon (obtained
six to eight weeks after conception) bilaterally to the caudate
and putamen in two immunosuppressed patients with severe MPTP-induced
parkinsonism, using a stereotaxic technique. The patients were
assessed regularly with clinical rating scales, timed tests of
motor performance, and [18F]fluorodopa positron-emission tomography
during the 18 months before the operation and the 22 to 24 months
after the operation. RESULTS. Both patients had substantial, sustained
improvement in motor function and became much more independent.
Postoperatively, the second patient's maintenance dose of levodopa
was decreased to 150 mg daily, which was 30 percent of the original
dose. Striatal uptake of fluorodopa was unchanged 5 to 6 months
postoperatively but was markedly and bilaterally increased at
12 to 13 and 22 to 24 months in both patients, closely paralleling
the patients' clinical improvement. There were no serious complications.
CONCLUSIONS. Bilateral implantation of fetal mesencephalic tissue
can induce substantial long-term functional improvement in patients
with parkinsonism and severe dopamine depletion and is accompanied
by increased uptake of fluorodopa by the striatum. The results
in these patients resemble those obtained in MPTP-treated primates
and suggest that this will be a useful model for the assessment
of transplantation therapies in Parkinson's disease.
- AN 93063065
- AU Freed CR.
Breeze RE. Rosenberg NL. Schneck SA. Kriek E. Qi JX. Lone
- Zhang YB. Snyder
JA. Wells TH. et al.
- IN University
of Colorado Health Sciences Center, Denver 80262. TI Survival
of implanted fetal dopamine cells and neurologic improvement 12
to 46 months after transplantation for Parkinson's disease [see
- SO New England
Journal of Medicine. 327(22):1549-55, 1992 Nov 26.
- AB BACKGROUND
AND METHODS. Patients with Parkinson's disease tend to have a
reduced response to levodopa after 5 to 20 years of therapy, with
"on-off" fluctuations consisting of dyskinesia alternating
with immobility. In an effort to modify the motor disability of
advanced Parkinson's disease, we implanted embryonic mesencephalic
tissue containing dopamine cells into the caudate and putamen
of seven patients. Two patients received unilateral grafts in
the caudate and the putamen on the side opposite the side with
worse symptoms. Five patients received bilateral grafts implanted
in the putamen only. In six of the seven patients, the fetal tissue
was obtained from a single embryo with a gestational age of seven
to eight weeks. The tissue was injected by means of 10 to 14 needle
passes. There were no surgical complications. Four of the seven
patients underwent immunosuppression with cyclosporine and prednisone.
RESULTS. All patients reported improvement according to the Activities
of Daily Living Scale when in the on state 3 to 12 months after
surgery (P < 0.01). Neurologic examination according to the
Unified Disease Rating Scale showed that five of the seven patients
improved when in the on state six months after surgery. The mean
group Hoehn-Yahr score improved from 3.71 to 2.50 (P < 0.01).
Computer and videotape testing in the home supported these findings.
Fluctuations in clinical state were moderated, and periods of
dyskinesia and off episodes were shorter and less severe than
before implantation. Drug doses were reduced by an average of
39 percent (P < 0.01; maximum, 58 percent). The results of
cliniical evaluation and fluorodop positron-emission tomography
in one patient were compatible with transplant survival for as
long as 46 months. Both immunosuppressed and nonimmunosuppressed
patients improved. CONCLUSIONS. Fetal-tissue implants appear to
offer long-term clinical benefit to some patients with advanced
- AN 93063064
- AU Spencer DD.
Robbins RJ. Naftolin F. Marek KL. Vollmer T. Leranth C. Roth RH.
Price LH. Gjedde A. Bunney BS. et al.
- IN Neural Transplant
Program, Yale University School of Medicine, New Haven, Conn.
- TI Unilateral
transplantation of human fetal mesencephalic tissue into the caudate
nucleus of patients with Parkinson's disease [see comments].
- SO New England
Journal of Medicine. 327(22):1541-8, 1992 Nov 26. AB BACKGROUND.
Parkinson's disease is characterized by the loss of midbrain
- dopamine neurons
that innervate the caudate and the putamen. Studies in animals
suggest that fetal dopaminergic neurons can survive transplantation
and restore neurologic function. This report compares the clinical
results in four case patients with severe Parkinson's disease
who underwent stereotaxic implantation of human fetal ventral
mesencephalic tissue in one caudate nucleus with the results in
a control group of similar subjects assigned at random to a one-year
delay in surgery. METHODS. Each case patient received cryopreserved
tissue from one fetal cadaver (gestational age, 7 to 11 weeks).
Before implantation, adjacent midbrain tissue underwent microbiologic,
biochemical, and viability testing. Cyclosporine was administered
for six months postoperatively. RESULTS. The procedure was well
tolerated. Three case patients showed bilateral improvement on
motor tasks, as assessed on videotape, and were more functional
in the activities of daily living, as assessed by themselves and
neurologists, during both optimal drug therapy and "drug
holiday" periods. One case patient, who died after four months
from continued disease progression, had striatonigral degeneration
at autopsy. In the patients who received transplants, optimal
control was achieved with a lower dose of antiparkinsonian medications,
whereas the controls required more medication. Positron-emission
tomography with [18F]fluorodopa before and after surgery in one
patient revealed a bilateral restoration of caudate dopamine synthesis
to the range of normal controls, but continued bilateral deficits
in the putamen. CONCLUSIONS. Although the case patients continued
to be disabled by their disease, unilateral intracaudate grafts
of fetal tissue containing dopamine diminished the symptoms and
signs of parkinsonism during 18 months of evaluation.
- AN 93044295
- AU Bjorklund
- IN Department
of Medical Research, University of Lund, Sweden. TI Dopaminergic
transplants in experimental parkinsonism: cellular mechanisms
of graft-induced functional recovery. [Review]
- SO Current Opinion
in Neurobiology. 2(5):683-9, 1992 Oct.
- AB The ability
of intrastriatal grafts of fetal mesencephalic dopamine neurons
to ameliorate the symptoms of experimental and clinical parkinsonism
has raised the question of the mechanisms underlying the transplant-induced
functional effects. Recent studies have taken advantage of quantitative
cytochemical and in situ hybridization techniques to study functional
graft-host interactions at the cellular level in the rat Parkinson
model. The results provide evidence that behaviorally functional
grafts restore dopaminergic neurotransmission and normalize dopamine
receptor function in the denervated striatum, and that these effects
are likely to depend on both synaptic and extrasynaptic mechanisms.
- AN 92246461
- AU Sawle GV.
Bloomfield PM. Bjorklund A. Brooks DJ. Brundin P. Leenders KL.
Lindvall O. Marsden CD. Rehncrona S. Widner H. et al.
- IN Medical Research
Council Cyclotron Unit, Hammersmith Hospital, London, England.
- TI Transplantation
of fetal dopamine neurons in Parkinson's disease: PET [18F]6-L-fluorodopa
studies in two patients with putaminal implants.
- SO Annals of
Neurology. 31(2):166-73, 1992 Feb.
- AB Two patients
with Parkinson's disease who underwent implantation of fetal mesencephalic
tissue into the putamen were serially studied using positron emission
tomography and [18F]6-L-fluorodopa ([18F]dopa). The uptake of
[18F]dopa is related to the functional integrity of the presynaptic
dopaminergic system. Preoperative studies revealed a marked decrease
in putamen [18F]dopa uptake, with lesser involvement of the caudate.
Two and 4 months, respectively, after operation, both patients
demonstrated functional improvement, as described elsewhere. One
patient was scanned 5, 8, and 13 months after the operation and
the other was scanned 7 and 12 months after the operation. In
both patients, [18F]dopa uptake increased within the operated
putamen despite a progressive decrease in tracer uptake in the
unoperated striatal structures. We believe that this increased
uptake of [18F]dopa at the implantation site represents functional
integrity within a surviving neural graft. While there has been
little further clinical improvement beyond the fifth postoperative
month, the uptake of [18F]dopa at the operation site in both patients
has progressively increased. The kinetic data provide evidence
of disease progression in the unoperated striatum, which, balanced
against increasing graft function, may explain why clinical improvement
reached a plateau within months after surgery.
- AU Lindvall
O. Widner H. Rehncrona S. Brundin P. Odin P. Gustavii B. Frackowiak
R. Leenders KL. Sawle G. Rothwell JC. et al.
- IN Department
of Neurology, University Hospital, Lund, Sweden. TI Transplantation
of fetal dopamine neurons in Parkinson's disease: one-year
- clinical and
neurophysiological observations in two patients with putaminal
- SO Annals of
Neurology. 31(2):155-65, 1992 Feb.
- AB Ventral mesencephalic
tissue from aborted human fetuses (age, 6-7 weeks' postconception)
was implanted unilaterally into the putamen using stereotaxic
surgery in 2 immunosuppressed patients (Patients 3 and 4 in our
series) with advanced idiopathic Parkinson's disease. Tissue from
4 fetuses was grafted to each patient. Compared with our previous
2 patients, the following changes in the grafting procedure were
introduced: the implantation instrument was thinner, more tissue
was placed in the operated structure, and the time between abortion
and grafting was shorter. There were no postoperative complications.
Both patients showed a gradual and significant amelioration of
parkinsonian symptoms (most marked in Patient 3) starting at 6
and 12 weeks after grafting, respectively, reaching maximum stability
at approximately 4 to 5 months; patients remained relatively stable
thereafter during the 1-year follow-up period. Clinical improvement
was observed as a reduction of the time spent in the "off"
phase and the number of daily "off" periods; a lessening
of bradykinesia and rigidity during the "off" phase,
mainly but not solely on the side contralateral to the graft;
and a prolongation and change in the pattern of the effect of
a single dose of L-dopa. Neurophysiological measurements revealed
a more rapid performance of simple and complex arm and hand movements
bilaterally, but primarily contralateral to the graft. The results
indicate that patients with Parkinson's disease can show significant
and sustained improvement of motor function after intrastriatal
implantation of fetal dopamine-rich mesencephalic tissue. The
accompanying paper by Sawle and colleagues describes the results
of repeated positron emission tomography scans in these patients.
- AN 89272713
- AU Lindvall
O. Rehncrona S. Brundin P. Gustavii B. Astedt B. Widner H. Lindholm
T. Bjorklund A. Leenders KL. Rothwell JC. et al.
- IN Department
of Neurology, University of Lund, Sweden.
- TI Human fetal
dopamine neurons grafted into the striatum in two patients with
severe Parkinson's disease. A detailed account of methodology
and a 6-month follow-up.
- SO Archives
of Neurology. 46(6):615-31, 1989 Jun.
- AB By using
stereotaxic surgical techniques, ventral mesencephalic tissues
from aborted human fetuses of 8 to 10 weeks' gestational age were
implanted unilaterally into the striata in two patients with advanced
Parkinson's disease. The patients were treated with a cyclosporine,
azathioprine, and steroid regimen to minimize the risk for graft
rejection. They were examined for 6 months preoperatively and
6 months postoperatively and continued to receive the same doses
of antiparkinsonian medication. There were no significant postoperative
complications. No major therapeutic effect from the operation
was observed. However, in the clinical tests, both patients showed
small but significant increases of movement speed for repeated
pronation-supination, fist clenching, and foot lifting. The rate
of walking also increased in the one patient tested. For both
patients, there was an initial worsening postoperatively, followed
by improvement vs preoperative performance at 1 to 3 months. Both
patients also showed significant improvement in the magnitude
of response to a single dose of levodopa (L-dopa), but there was
no increase in the duration of drug action. The motor readiness
potential increased in both patients postoperatively, primarily
over the operated hemisphere. Neurophysiological measurements
also showed a more rapid performance of simple and complex arm
and hand movements on the side contralateral to transplantation
in one patient at 5 months postoperatively. Positron emission
tomography demonstrated no increased uptake of 6-L-(18F)-fluorodopa
in the transplanted striatum at 5 and 6 months. Taken together,
these results suggest that the fetal nigral implants may have
provided a modest improvement in motor function, consistent with
the presence of small surviving grafts. Although our results support
further scientific experimentation with transplantation in Parkinson's
disease, widespread clinical trials with this procedure are probably
not warranted at this time.