FROM: Wall Street Journal

New Test May Detect Parkinson's Early, Aid Search for Drugs
by Scott Hensley.
 Wall Street Journal (Eastern Edition).
Jan 7, 2005.  p. B.1

"WHEN PARKINSON'S disease progresses far enough, the symptoms are as
heartbreaking as they are unmistakable: trembling in the limbs,
difficulty
controlling movement, and even, eventually, paralysis.

But in the early stages of the disease, telltale signs are tricky to
spot. One
doctor seeing a patient with infrequent blinking or a slight tremor will
diagnose Parkinson's, while another might dismiss those symptoms as
nothing to
worry about. By the time unambiguous symptoms emerge, Parkinson's has
usually
been on the attack for years, destroying 60% or more of the special cells
in
the brain that control voluntary movement.

Now scientists at drug giant Pfizer think they have stumbled on a simple
test
that is both sensitive enough to detect subtle biological changes due to
Parkinson's and specific enough to avoid false alarms: analyzing how
people
speak. If further studies confirm their conclusion, the test could offer
a more
accurate way to diagnose Parkinson's before large numbers of brain cells
are
irreversibly lost, and speed the development of new drugs for the
disease.

With many illnesses, particularly those of the nervous system, doctors
make a
diagnosis by eliminating alternatives. Even with advances in brain scans,
they
rely primarily on questionnaires, physical exams and intuition to
identify
common disorders, such as Alzheimer's, as well as rarer ones, including
Parkinson's.

THE PFIZER RESEARCHERS wondered if they could do better. Rather than draw
blood
or even spinal fluid, they believed it might be possible to detect the
illness
by analyzing speech patterns. In Parkinson's, the characteristic decline
in
muscle control stems from the loss of dopamine-producing nerve cells in
the
substantia nigra, a compact region in the middle of the brain. Building
on
insights from other scientists, Pfizer researchers reasoned that
hesitation and
hitches later seen in the movement of large muscles might be apparent
earlier
in shaking or trembling of the tiny muscles involved in speech, including
the
vocal cords.

In 2001, Pfizer neuroscientist Peter Snyder and colleagues began working
with a
computer system to analyze the variability of speaking tone and the
length of
pauses between consonants and vowels. To test their techniques, the
researchers
searched news databases for public figures diagnosed with Parkinson's, a
group
that includes actor Michael J. Fox, former Attorney General Janet Reno
and
boxer Muhammad Ali. They focused on two people whose dates of diagnosis
were a
matter of public record and for whom there were plenty of voice
recordings made
years before as well as after the illness was identified.

The subjects, aged 42 and 65 in 2003, haven't been named publicly because
of
rules about patient privacy. Two other people matched by age and
profession but
with no known history of neurological problems served as comparison
subjects.

Using a commercial voice-analysis computer program, the Pfizer scientists
evaluated interviews in CNN's video archives. They found the Parkinson's
patients spoke in slight monotones years before they were diagnosed,
though the
changes were so slight they weren't detectable by the human ear. A
subsequent
test confirmed the findings in four patients recently diagnosed with
Parkinson's. The results appeared in the Journal of Neurolinguistics in
November.

THE PARKINSON'S VOICE test takes about seven minutes and requires
equipment
costing only a few thousand dollars. For the moment, the scarcity of
treatment
options for patients with mild Parkinson's limit the usefulness of an
early
warning about the condition. "If you can't do anything about it, why tell
people they have the disease?" says Howard Hurtig, a neurologist at
Pennsylvania Hospital in Philadelphia.

Nevertheless, research into reliable diagnostic markers of Parkinson's
disease
is drawing increased funding from the National Institutes of Health. The
Michael J. Fox Foundation launched a $2 million program in November to
search
for biological markers. "It's probably early to say that this acoustic
approach
would work," says Brian Fiske, a scientific manager for research programs
at
the foundation. But "there's a definite need for a good biomarker that
would
allow you to diagnose Parkinson's disease at an early stage," especially
for
drug development.

Pfizer has no plans to market the speech test but may explore licensing
the
technology to other companies. Its ultimate goal is to find drugs that
would
change the course of Parkinson's and related diseases by protecting nerve
cells. As things stand now, the lack of a standard test for Parkinson's,
like
blood sugar for diabetes, stymies efforts to gauge the effect of
experimental
drugs. "If symptoms are mild and you're treating early, then how do you
know if
your treatment is working?" asks Pfizer's Dr. Snyder.

He acknowledges that his method must be validated in further tests before
it
can be used routinely. But in the meantime, his team has successfully
applied
the speech test to patients with depression and schizophrenia, which can
also
involve abnormal levels of dopamine in the brain."

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