Lanier,

I'm sorry that you are leaving the list due to all the stem cell talk
and politics. Although I sick of it too, it's important that we discuss
this within the Parkinson's community so that we can make informed
decisions.

Unfortunately, the U.S. federal government out spends the private sector
by orders of magnitude for Parkinson's research. Congress appropriates
the funds and our activism keeps congress focused on our needs. This is
the way I anticipate that it will continue unless list members over
throw the government and make me king. (Note to the FBI  and National
Secuirty Agency. I'm just kidding.)

Research institutions want to do leading edge, high visibility research.
Bio-tech is a hot field and research institutions want to be associated
with this emerging field. It is the type of stuff that will bring in
federal grant money as well as private endowments for research wings. In
addition, top notch researchers will find another institution if they
don't get their way. So that is why you will get prestigious
institutions like Harvard Medical School lobbying for embryonic stem
cell research. So it's about money. Money comes from the federal
government and appropriations are political.

So this makes it very important that we understand the science of
embryonic stem cell research so that we can make our voices heard as a
community and as individuals both pro and con in an informed and
intelligent manner. Eveyone has a right to express their own scientific,
moral and religious beliefs. We then rule by majority which means there
will always be a group that will be unhappy and sometimes abusive. It
also means that there will be groups lobbying on capitol hill claiming
that they represent the majority.

Now for my humble opinion. Embryonic stem cell research will some day
lead to a cure for Parkinson's just like atomic fusion will some day
elimnate our dependence on foreign oil. At 54, I guess it could happen
in my lifetime, but I'm not betting my 401K.

So what do we risk by being the poster children for embryonic stem cell
research? Right out of the box we alienate a portion of congress and
their constituency. As long os one of these members isn't on the
appropriations committee, it might not be so bad. And who needs the
constituency if we're getting big bucks from the federal government. So
we get the big bucks sent to NIH ear marked for PD and they distribute
it. Since we are the poster children for embryonic stem cell research,
we must want all these funds to go into basic science for stem cell
research. This leads to a cure for PD and we all live happily ever
after.

So what's wrong this fairy tale? To begin with Parkinson's isn't a
disease, it's a set of symptoms. It's idiopathic. We don't know how many
pathologies (diseases) eventually will produce these symptoms. In lay
terms it's a designer disease. Everyone seems to be a little different.
But I'm sure some of you are saying Phil, you idiot these symptoms are
caused by death of cells in the substantia nigra that produce dopamine.
Of course probably less than 1% of the PD population has had a PET scan
to confirm that there is indeed a reduction in uptake of dopamine. So
our diagnosis can be and sometimes is wrong. But Phil, if stem cells are
used to regnerate those cells we're cured and can ride off into the
sunset. Unfortunately, the stem cell work done to try this resulted in
uncontrolable dyskinesias and psychosis in some patients, the same as
that seem with high doses of levodopa.

So unlike diabetes, it isn't just a chemical deficiency. In fact, what
we also lose is the projections from the substantia nigra into the
striatum (caudate and putamen) that carry the dopamine produced in the
substantia nigra to the striatum. These projections constitute part of
the front end wiring into the basil ganglia. Now since one neuron can
project onto as many as 1000 other neurons, these interconnections can
be quite complex. Indeed as the nervous system develops, some pathways
are exercised more and become stronger while others die off. This is
effectively how the nervous system programs itself not only during
gestation, but also during early childhood development. So now that we
have that figured out, we can get stem cells to regenerate the wiring
and then we can reprogram it to restore function.

So let's get started with the programming specification for the basil
ganglia. So let's write down the functions that the basil ganglia
perform. Well obviously PD is a movement disorder so it must control
movement. But in normals fMRI has shown that activity in the basil
ganglia begins before the movement is initiated and teminates when the
movement starts. But in PD patients, the activity in the basil ganglia
continues throughout the movement. So it seems to be crucial that we
understand the differences in the wiring between the controls and the PD
patients. Although everyone is in the brain donation program, we'll need
to wait years before enough of these geezers die off to really come up
with the cure.

But wait, we have the technology to remove the genetic material from one
species and replace it with the genetic material from a second species
and then return it to the original host for gestation. In this way, we
can sacrifice these fetuses at different points in their gestation and
learn how the basil ganglia develop. We can then use this knowledge to
program the repaired basil ganglia and cure PD. Hopefully, we won't
have to allow the fetus to develop too far during early childhood
development before we discover how to program the basil ganglia.

So we have fixed the movement disoder. Now about 43% of the PD
population seems to suffer from disorders of the autonomic nervous
system. This system controls things like heart rate, respiration,
temperature control (sweating), etc. The basil ganglia don't appear to
be wired to the autonomic nervous system. But since the stem cell fairy
can fix anything, I'm sure she will fix this too.

Now to other non-motor features of PD. In the range of 40-60% of PD
patients develop mood disorders. These appear to be associated with
reduced levels of seretonin and norepinephrine. Compared to the motor
aspects of PD, these psychiatric features have been poorly studied.

About 30% of PD patients will eventually develop cognitive disfunction.
This appears to be related to reduced levels of acetycholine. Although
it is known the basil ganglia do play some role in cognitive processing,
the nature of this role is even less understood than their role in
movement. This is another highly under investigated area.

A year and a half ago, a representative from PAN came in and told our
support group that a cure from PD was five years away if congress
appropriated the funding for research. Even with my limited knowledge
about PD, I had to question the validity of that projection. The PAN
representitive indicated that it come from a researcher testifying
before congess lobbying for an increase in funding. I left the meeting
scratching my head. Why hadn't I seen anything about this in the
literature?

This year the PAN respresentative was promoting advocacy for stem cell
research and had brought along a neurologist to technically support her
position. When I indicated that I had difficulty supporting embryonic
stem cell research since I didn't feel that the ethical stands were in
place to properly manage this research, I was almost jeered by part of
the attending membership. At the end of the meeting, the neurologist
thanked me for speaking up and indicated that he agreed with my
position. Once again, I left the meeting scratching my head.

So my humble opinion of embryonic stem cell research is that it is a
solution looking for a problem to solve. Unfortunately, if we use all
our PD allocated dollars to learn how to morph stem cells, we won't have
the dollars to investigate the pathologies of the motor and non-motor
features of PD. We'll have a cure, but a cure for what?

So to me the issue is not about re-cycling the refuse from fertility
clinicals, but what is the ethical use of that refuse. And in the grand
zero sum game of funds allocated to PD research, how much of those funds
should be allocated to basic stem cell research and how much to the many
other aspects of the disease that need to be investigated before we will
really have a cure.

So Lanier and others, you can leave the list, but please become
knowledgable and make your opinions known. Otherwise, all you can hope
for is that the basil ganglia fairy will leave some stem cells under
your pillow.

Good night.

The humble Phil Gesotti

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