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The following is a paper on the fetal transplant program at the Hospital of
the Good Samaritan at Los Angeles.
 
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Two-year Experience of Fetal Mesencephalic Tissue Transplants
Deane B Jacques, M.D.  Oleg V. Kopyov, M.D., Ph.d., The Good Samaritan
Hospital
 
The data accumulated during the last decade from both animal and preliminary
human clinical transplantation of ventral mesencephalic fetal tissue offers
the promise of ameliorating the kinetic symptomatology of Parkinson's Disease
(PD), especially among patients who are refractory to pharmacological
treatment of the disease.  A large number of PD patients who have been on
levodopa therapy for extended periods of time eventually show reduced
responsiveness to the drug and eventually develop severe disabling symptoms.
PD has received a majority of the attention in neurotransplantation programs
because of the strong relationship of this disease to the single
neurotransmitter, dopamine (DA).
 
Early histologic studies were able to demonstrate a loss of DA-producing
cells in the substantia nigra among PD patients.  This, combined with
substantial evidence that pharmacological replacement of DA results in
reduced somatic anomalies, suggests that intracerebral replacement of
DA-secreting cells has the potential to benefit these patients.
 
One of the major goals of the neurotransplantation program at the Hospital of
the Good Samaritan was to develop a new technique for treating PD by
implantation of fetal ventral mesencephalon (FMV) into the human striatum.
In our study we have tried to show that refined surgical technique, optimized
handling and processing of fetal tissue, and careful patient selection are
the key elements of successful neurotransplantation.
 
Eight men and three women with idiopathic PD (Hoehn and Yahr stage 3-5)
underwent fetal brain tissue transplantation using MRI-guided stereotaxis.
Clinical evaluations were performed by Professor of Neurology Charles M.
Markham (UCLA, Los Angeles) every three to four months several times
pre-operatively and at the same intervals post-operatively, consisting of
neurological and brief general physical exams, UCLA Parkinson's Disability
Scale, Hoehn and Yahr rating, and Unified Parkinson's Disease Rating Scale,
all in both "on" and "off" states.  Timed tests of walking, hand and foot
dexterity and video recordings were made, and self-ratings of symptoms and
dyskinesia were completed for seven consecutive days prior to each visit.
Fluorodopa PET scans were performed by Barry Snow, M.D. and F. Vinghoets
(University of British Columbia) on six patients pre-operatively five to six
months and 13 to 15 months post-operatively.
 
A novel hydraulic system was employed to implant solid pieces of fetal
ventral mesencephalon of about 0.5-1.0 cubic mm into three needle tracks in
the putamen and one needle track in the caudate.  Eight patients were
operated on unilaterally and three, bilaterally.  Each patient received 8-21
pieces of brain tissue (total volume of the implanted tissue is approximately
4-12mm) from one to two human fetuses of seven to nine week's gestation and
was given immunosuppressants for 18 months post-operatively.  Levodopa was
decreased post-operatively to avoid possible injury to fetal tissue and was
later gradually increased to optimal level.
 
Four men and two women are distinctly improved at two years post-operatively.
Their mean age at transplantation was 49 years; mean disease duration was
13.6 years.  Two of these patients received bilateral implants.  One of these
two patients discontinued antiparkinsonian medication.
 
One woman and three men have not improved.  Two of these patients are
currently on 60% to 70% of their preoperative medication.
 
All patients of the unimproved group showed no progress of their PD during
two to two and one-half years post-operatively.  Mean age of the unimproved
patients at transplantation was 58.4 years; mean duration of disease was 11.8
years.
 
Our bilaterally-operated patients experienced pronounced inactivity in the
immediate postoperative period.  Recently, we operated on six patients
bilaterally, employing somewhat different surgical and post-operative
tactics: 1) All needle, tracks (3-4) were placed in the posterior putamen
only; 2) after surgery the pro-operative level of medication was maintained,
and only 7-10 days later, we began decreasing levodopa medication; 3) total
volume of the implanted tissue was raised up to 25 cubic mm.
 
No one of these patients experienced the above-mentioned post-operative
immobility.  All of them showed different signs of improvement on the third
or fourth day post-operatively.  Our results show that age at operation may
be a determinant of outcome.  Stereotactical targets and amount of the
implanted tissue also noticeably affect post-operative regression of
Parkinson's Disease.
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Greg Johnson
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