Brain Transplant:
1994 NOVA Documentary
Follow up
List of Methods
Behavioral
Various tests of motor function - pupillary reflex, walking, sitting, standing,
talking, finger touching, balance (from a push), blinking (tap of forehead),
rigidity (movement of wrist or limb)
Nervous system
L-DOPA and other drug treatments (e.g., neuroprotection)
Chemical identification of MPTP
Adrenal tissue to brain transplant
Animal model of PD using MPTP
Nerve graft tissue transplant in monkeys and humans
Dissecting fresh fetal nerve cells from substantia nigra
Stereotaxic surgery –
intracerebral injection of fresh tissue suspension
into caudate and putamen (striatum)
postoperative care (baseball game)
immunosuppression therapy
PET scan of flora-dopa uptake in striatum and
Estimation of percentage of graft secreting dopamine
Follow-up questions
Given that it took George and Juanita two
years to show miraculous recovery, what
was the status of Connie at this time point
following surgery?
Are there any more recent reports of her
progress, or lack thereof?
What is her present condition?
Why didn’t NOVA report on her progress as
promised in the documentary?
JOURNEY OUT OF HOPELESSNESS GREENFIELD
WOMAN THANKS READERS WHOSE DONATIONS
RESTORED HER HUMANITY
from PARKINSN Archives: Sun, 28 May 1995
Langston, the renowned Parkinson's disease
scientist, described the essence of Connie's
improvement this way:
''What makes you human is the ability to interact
with other humans. If you lose that, and Connie
had, you lose the essence of life. It takes away
what makes you a person. Connie is still very
disabled, but she has regained her humanity.
She is no longer a statue in the corner.''
Local news report from 1995, a year after
Connie’s transplant
Writer Jim Trotter at the Mercury News
Two years ago, when I drove down with Langston from the Parkinson's
Institute to visit Connie in Greenfield, the scene was far different.
Sophisticated computer testing indicated that she was still cognitive,
that her brain comprehended, beyond the frozen mask. But even
with the aid of elaborate computer switches, she couldn't
communicate.
Now she is a smiling human being who can walk a bit and respond to
questions. Surgery to reattach her ankle ligaments will greatly
enhance her mobility. But Langston said overcoming language
''ignition failure'' -- the inability to talk spontaneously in expressing
one's thoughts -- will take more time. ''But when that happens, she
will really be back,'' he said.
I could not resist sitting down next to Connie and telling her how much I
admired her courage. She turned her eyes and said, ''Thank
you.'' Don't give up, I said. Painstakingly, but clearly, she
responded. ''I won't.''
Symptoms of PD
1) resting tremor (rhythmic shaking of an extremity),
2) slowness of movement (hypokinesia or
bradykinesia) - movements take much longer to execute
and there is also a general lack of movement (akinesia),
3) cogwheel rigidity (arms and legs become stiff with a
ratchet or jerky quality of movement - almost no other
disease produces this symptom),
4) slow shuffling gait, short steps with the patient bent
or flexed over (very characteristic of PD) and
5) loss of facial expression and lack of spontaneous
blinking which gives the appearance staring.
L-DOPA treatment
Reversed symptoms but the therapeutic window closed as
severe side effects set in – hallucinations, dyskinesia, and
uncontrollable movement
“Parkinson’s disease is not caused by transient
exposure to MPTP”
That is, only f you use
a strict neurobiological
marker as the
criterion.
The similarities in
behavioral changes
suggests strongly that
MPTP exposure
replicates virtually all
the behavioral
symptoms of PD.
Radiolabeled FD uptake in the striatum
Normal
PD
PD – reduced uptake in the
putamen
MPTP – uniform reductions
in both the caudate nucleus
and putamen
Moderate
MPTP
Severe
MPTP
NIH-sponsored placebo controlled trials
Winkler et al, 2005
Figure 1. Functional recovery after neural transplantation in Parkinson’s
disease (PD). Recovery is suggested to occur in two phases: phase one is
characterized by functional changes limited to the striatum, whereas in
phase two changes of cortical activation can also be detected.
Winkler et al, 2005
Figure 2. Allografts of
fetal dopaminergic
neurons are
accompanied by a
delayed immune/
inflammatory
response, which
could affect longterm survival and
functional efficacy
of the transplanted
dopaminergic
neurons.
variability in individual outcomes in the open label
studies suggest that other factors might contribute
to the success of the treatment.
1) preparation and composition of the graft tissue - prolonged
cold storage and use of solid grafts are not as good
2) selection of patients - older patients do not tend to benefit as
much as young patients due to less confined damage and
reduced ability to accept to graft
3) pre-graft medication – low-dose patients tend to benefit more
from graft. In fact, one of the controlled studies with older
patients with no significant group improvement there was a
correlation between the magnitude of the response to dose of Ldopa and the magnitude of the postsurgical improvement.
4) graft placement – grafts only innervate tissue 2-3 mm from the
graft site so benefits will depend on the location of the
placement and whether there is limited damage outside of the
striatum.
The authors conclude that standardized procedures for
selection of patients, graft preparation and
immunosuppresion, combined with tailoring the placement
of grafts may improve the outcome of this promising
therapy for PD.
MPTP exposure initiates long-term neurodegeneration
Practice questions
Where was the fetal tissue taken from and
where was it transplanted to?
Immunosuppresion is important for postsurgical improvement to occur in the first 6
months or after that time.
What was shown to be a misconception
regarding MPTP exposure and why?
What data suggests that MPTP does not
induce PD?