Parkinson's Disease-Causes, Treatment and Recent Research Findings

Novel Treatment for
Parkinson's Disease

Researchers from University of Missouri have identified the role of
alpha-synuclein in Parkinson's symptoms. When alpha-synuclein
becomes mutated and clumps at the cell surface, it manages to drag
away a protein that helps transport the ER and the Golgi Bodies. This
gives a new direction for considering much better treatments, e.g. gene
therapy, for people suffered from Parkinson's Disease. {A}

ABOUT PARKINSON'S DISEASE
More than a million Americans suffer from Parkinson's Disease, So far,
no current therapies alter the fundamental clinical course of the
condition.

Parkinson's Disease is a progressive deterioration of neurons in the
midbrain. That deterioration, in turn, leads to a shortage of the chemical
messenger dopamine, resulting in muscle rigidity, impaired movement,
and uncontrollable shaking of limbs. The most common treatment for
Parkinson's Disease is the oral administration of the dopamine
precursor, L-dopa. L-dopa subsides the symptoms at first, it becomes
ineffective over the time.

Tatyana Sotnikova et al, Duke Universtiy, screened potential
therapeutic drugs using a mouse model. By eliminating the dopamine
transporter-the protein responsible for recycling the chemical into
neurons-in mice, the researchers reduced dopamine levels in the
midbrain by 20-fold. This inhibition of dopamine production resulted in
essentially unmeasurable levels of the neurotransmitter. Dr. Sotnikoya
and his group found that in addition to L-DOPA-related treatments,
drugs related to amphetamine were effective in ameliorating muscle
rigidity, tremor, and impaired movement in these mice.

The most effective was methylenedioxymethamphetamine HCl (MDMA),
commonly known as ecstasy. It has been shown that amphetamines can
trigger release of neurotransmitters such as dopamine, serotonin, and
norepinephrine and cause sudden bursts in neurotransmission, leading
to a feeling of alertness, increased muscular activity, and reduced
fatigue. But MDMA did not raise dopamine levels, hinting that it restores
movement through an unknown mechanism outside of the dopamine
system.

The team also found that a combination of MDMA and the current
Parkinson's drug L-DOPA, a chemical building block of dopamine was
more effective than either drug alone.

"This suggests that maybe low concentrations of these amphetamines,
or compounds related to them, could be potentially used as add-ons to
L-DOPA," says Caron. The study is reported in PloS Biology1.

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Citation: Sotnikova TD, Beaulieu JM, Barak LS, Wetsel WC, Caron MG, et al. (2005)
Dopamine-independent locomotor actions of amphetamines in a novel acute mouse model of
Parkinson's disease. PLoS Biol 3(8): e271.
[A] Researchers reverse Parkinson's symptoms in animal models EurekAlet June 22 2006.

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