Supplemental data for:
Luquin et al. Neuron 22, 743-750.
Parkinson’s disease is the second or third most common
neurodegenerative disorder, striking 1% of the population over age 65 (an even
greater
percentage in later decades). L-DOPA therapy provides symptomatic relief during
the early
stages of the disease but does not affect disease progression or ameliorate the
cognitive
deficits. Transplantation of fetal mesencephalic neurons (using tissue from up
to ten fetuses
per transplant patient), however, has been effective in retarding the
progression of the
disease in some patients. Unfortunately, the logistics (not to mention the
ethical issues
involved) of a low transplant efficiency (less than 20% of the transplanted
dopaminergic
neurons survive), and the requirement for immunosuppression to prevent graft
rejection,
have made this approach impractical for the majority of severely affected
patients. The other
remaining treatment strategies have centered around lesions of the thalamus or
globus
pallidus to compensate for the imbalance of activity that results from loss of
striatal
dopaminergic neurons; unfortunately these lesions are not successful in
amelioriating tremors
and symptoms often recur with time.
In the February 1998 issue of Neuron, Espejo et al. provided exciting evidence
that
dopamine-secreting cells from the carotid body can be transplanted into
parkinsonian rats to
cause a dramatic functional recovery of almost all the deficits produced by the
6-hydroxy
dopamine lesion. In the April 1999 issue of Neuron, Luquin et al. take a large
step toward
making autotransplants a viable option for humans, especially those with
bradykinesia. In this
study, they demonstrate that chronically MPTP-treated macaque monkeys (with
bilateral
striatal lesions) that receive autotransplants of carotid body cell aggregates
to the left
putamen (a region of the striatum) show striking improvements in mobility, and
fine motor
tasks of the right hand (controlled by the hemisphere that received the
transplants) lasting up
to 5 months after transplantation. Unlike the preceding study in rodents (which
do not
tolerate bilateral striatal lesions), which could not rule out recovery arising
from migration of
tyrosine hydroxylase-positive neurons from the unlesioned hemisphere to the side
of the
transplanted carotid body cell aggregates, this study demonstrates an increase
in tyrosine
hydroxylase positive neurons only in the side that received the carotid body
grafts. The use of
cells of the carotid body is a creative experimental strategy for circumventing
the problem of
low transplant efficiency, since these cells normally function to sense low O2
levels in the
blood and thus are likely to be hearty in poorly vascularized transplants.
Intrastriatal autografts of carotid body tissue for treatment of Parkinson’s
disease may offer
several advantages. They are technically simple (compared to the other surgical
therapies of
pallidotomy, thalmotomy, or implantation of a high frequency stimulator),
require only part
of one carotid body, and do not cause side effects since humans can function
well with the
spared carotid body. This study shows short-term amelioration in a primate
model of
Parkinson’s disease. Further studies are needed to determine the longevity of
the recovery in
MPTP-treated primates with bilateral striatal autotransplants, and ultimately
whether this
therapy is viable in humans.
--
............................................................................................
Ray Strand
mailto:[log in to unmask]
............................................................................................
...on the edge of the prairie abyss ......................
