BRAIN INFUSION FOR PARKINSON'S DISEASE
STOCKHOLM- Natural proteins derived from brain cells may
offer a new therapeutic approach to neurodegenerative diseases
such as Parkinson's disease, report researchers.
Parkinson's disease results from a loss of cells in the area
of the brain called the substantia nigra. This in turn results in
a depletion of the neurotransmitter dopamine. While
neuroscientists understand something about what is happening in
the substantia nigra, very little is known about why it happens.
One hypothesis is that Parkinson's is caused by a lack of
sufficient dopaminotrophic support. Researchers at the Karolinska
institute in Stockholm conducted a series of experiments in mice
using a cloned version of a natural protein associated with nerve
cell growth called glial cell line-derived neurotrophic factor
(GDNF) to test this hypothesis.
One of the most important events in the history Parkinson's
disease research resulted from the unfortunate experience of a
handful of drug abusers in the San Francisco bay area. The drug
users had appeared at local medical centers with symptoms of
Parkinson's disease (tremors etc.) after taking a new designer
drug called MPTP. Animal studied showed that the drug had a
potent and specific neurotoxic effect on dopamine producing brain
cells, leading to the understanding that Parkinson's disease was
a problem of dopamine deficiency.
Since that time, MPTP has been used in animal studies to
induce Parkinson's-like brain deterioration. The Swedish
researchers injected GDNF into the brains of mice and then later
injected them with the MPTP toxin. The GDNF injection provided
impressive protection from the effects of the toxin. When GDNF
was administered after injection of the toxin, much of the
destructive effects of the toxin were reversed and dopamine
"We conclude that intracerebral GDNF administration exerts
both protective and reparative effects on the nigrostriatal
dopamine system, which may have implications for the development
of new treatment strategies for Parkinson's disease," notes Dr.
Lars Olson of the Karolinska Institute
Another group of researchers conducted a similar series of
experiments. However, instead of using a neurotoxin to impair
dopamine production, they transected axons i the forebrains of
rats. Left untreated, the result was a significant loss of
dopamine producing neurons in the substantia nigra. However, with
repeated injection of GDNF adjacent to the substantia nigra ,
this neuronal loss was largely prevented.
"Our findings show that GDNF can prevent the degeneration of
dopaminergic neurons in the adult mesencephalon, suggesting a
potential usage for GDNF in therapeutic approaches to Parkinson's
disease. GDNF so far is the only identified factor with highly
potent trophic activity on dopaminergic neurons in vivo," noted
Dr. Klaus Beck, department of neuroscience, Genentech.
Two other research groups reported that GDNF appeared to
protect nerve cells involved with muscle function, suggesting the
protein might also prove useful in the treatment of a number of
degenerative disorders including Lou Gehrig's disease
(amyotrophic lateral sclerosis).
All four of these studies appeared in Nature, v.373,
Nearly one million people in the U.S. have Parkinson's
disease. This is a mysterious disease with no known cause or
cure. The cause of Parkinson's disease is currently thought to be
a combination of environmental and genetic factors.
The symptoms of Parkinson's disease were first described by
British physician Dr. James Parkinson in 1812. The first symptom
is often an involuntary tremor. As the disease progresses, the
muscles become stiff and the face loses all expression. Patients
also develop difficulty walking and standing.
The first treatment breakthrough came with levadopa. The
drug essentially replaces the lost dopamine in the brain.
However, large doses are required, resulting in undesirable side
effects, such as nausea, heart problems & dementia. The
subsequent development of carbidopa, which is given in
conjunction with levadopa, allows a smaller dose of levadopa to
be used, resulting in fewer side effects.
Many patients respond well at first to this combination
therapy, but after a couple years of treatment the effects may
begin to wear off. At the same time, prolonged use of levadopa
can have serious side effects including involuntary movements of
the limbs and psychological disturbances.
A new treatment called seligiline has recently become
available which has a completely different mechanism of action
from levadopa. The drug is potent inhibitor of an enzyme called
'monoamine oxidase B' which breaks down dopamine. This means more
dopamine can be preserved in the brain. The drug appears to have
a neuroprotective effect and may delay the onset of Parkinson's