SCIENCE
Parkinson’s Disease
By Dr. Rizwana Rahim
Chicago, IL
Parkinson’s
disease (PD) is basically a chronic and progressive
condition of the central nervous system (CNS), named
after the British doctor, James P., who described
the disorder in considerable detail in 1817.
In PD, cells (neurons) in a certain section of the
brain called substantia nigra that produce a chemical
messenger called Dopamine (DA), are damaged or are
increasingly lost. DA is a brain chemical that signals/transmits
or carries messages (neurotransmitter) that ultimately
directs movement in different parts of the body,
including the limbs. Along with DA loss, the affected
neurons also carry clumps called Lewy bodies, the
pathological evidence of PD, and these toxic bodies
contain a mysterious protein, alpha-synuclein.
Loss of DP causes motor-system disorders, including
PD, that make the patients unable to direct or control
their normal movements. Early PD symptoms may be
confused with various age-related conditions and
vary from individual to individual, and may take
time to appear but are often quite unmistakably
noticeable, and include trembling or tremors in
hands and legs, difficulty in simple tasks like
walking or keeping balance and talking, stiffness
in body and limbs, with a progressive overall slowing
down of movements (or bradykinesia).
Progressive damage to neural cells is a feature
that PD shares with other neurodegenerative diseases,
such as Alzheimer’s and Lou Gehrig’s
(Amyotrophic lateral sclerosis; ALS). In Alzheimer’s,
the cerebral cortex and hippocampus are atrophied
(lose mass), which results in loss of cognitive
functions (memory, reasoning) and pattern recognition,
(neuritic plaques, neurofibrillary tangles and reduced
acetylcholine levels being the distinguishing features).
ALS is a neuromuscular disease in which the motor
neurons are destroyed, resulting in problems with
skeletal muscles (walking etc).
About 50,000 people are diagnosed with PD every
year. Since in some, it goes unrecognized for a
long time or early symptoms are not noticeable,
or are not diagnosed as PD, it is suspected that
a million Americans may have this disease. PD seems
to be an equalizer of a sort: it occurs in every
race, ethnic group, economic class, geographical
region or country, and strikes women and men almost
equally.
Age seems to be a major risk factor for PD. Most
PD patients are 50 years or older (average age 60),
but it is also known to strike people younger than
40 (e.g., actor Michael J. Fox, an early on-set
case). Another risk factor may be genetic (‘runs
in the family’ situation), because 15-20%
of PD patients also had a close relative with the
same disease.
Long-term exposure to pesticides seems to be an
environmental factor that increases the risk of
PD. In a recent survey of 143,000 people, a Harvard
team found that, regardless of occupation, pesticide
exposure boosted long-term Parkinson's risk by 70
percent over the long-term. Another survey of possible
dietary role in PD suggested that increased vitamin
B6 or pyridoxine consumption may lower the risk
of PD. Several studies also showed that smoking
can reduce the risk of getting PD, which is attributed
to the protection of brain cells by nicotine. Another
study published this year in ‘Neurology’
found that smokers who also took higher doses of
B6 had a lower risk of developing PD, and this protective
effect wasn’t seen in non-smokers.
However, most scientists believe PD may be due to
a combination of genetic and environmental factors.
Among the genetic leads for PD, the most promising
seems to be the gene that produces alpha-synuclein.
Abnormal quantities of this protein are found in
the affected neurons. Over-expression of this gene
(i.e., over-production of alpha-synuclein) and its
variants is also a rare cause of PD; a three-fold
increase in alpha-synuclein was seen in a recent
study. There is some association between the amount
of the gene (1 or 2x the normal) and PD’s
on-set age, rate of its progression and severity.
Rarely (in 1% cases), several mutations in this
gene also cause PD. In a large collaborative study
published in the 9 August issue of Journal of Medical
Association, the length of the REP1-promoter in
the gene was found to vary with the increase in
PD risk and the age of its onset.
No cure exists for PD, except that some drugs now
in use tend to slow down or stop its progress and
severity. The first drug approved (in 1970s) against
PD was levo-dopa (L-Dopa), which is still used (in
the brand, ‘Sinemet’). L-Dopa is taken
up by the neurons and is metabolically converted
there into DA. Increased DA level significantly
improves the PD symptoms, but as the diseases progresses,
L-Dopa dose will have to also increase. L-Dopa has
some side effects, including involuntary movements
and tics (dyskinesia) and hallucinations. Carbi-dopa
slows down the enzymatic conversion of L-Dopa to
DA in the blood, increasing the DA supply to the
brain, which prolongs the effects of L-Dopa and
reduces the side effects. A few other drugs (Comtan,
Deprenyl, Tasmar) inhibit this enzymatic conversion
of L-Dopa to DA, which also helps maintain a high
DA supply in the brain. Other drugs (Parlodel, Requip,
Permax, Mirapex) imitate DA (i.e., its agonists),
and are used along with L-Dopa. Some muscarinic
antagonists like Artane, Cogentin are particularly
effective for tremors. Symmetrel also helps the
tremors and increases L-Dopa effects. But all drugs
have adverse side effects, like mental confusion,
hallucinations, and dyskinesia.
There are some surgical options too, but after all
the non-invasive therapeutic approaches are exhausted,
and mostly depending on the patients’ physical
condition. Pallidotomy, i.e., a tiny hole drilled
into the skull to electrically destroy a small part
of the global pallidus that is believed to be overactive
in PD patients may help reduce dyskinesia caused
in some people by the drugs. Thalamotomy (destruction
of a group of cells in the thalamus) could help
disabling tremors, but not any other symptoms. Instead
of destroying tissue, a relatively new but less-used
technique, deep brain stimulation (DBS), can send
electric pulses (like pacemakers for the heart),
via electrodes implanted in the pallidus or subthalamic
nucleus, to block PD signals. Fetal tissue transplants
have been tried, but they are very risky, and face
ethical objections. Human stem cells (both embryonic
and adult) offer a lot of hope but the research
on it is mired in a lot of political, ethical debate,
and it may take many years before it can be of any
clinical use.
Despite a few advances in PD therapies and research
so far, PD remains, unfortunately, an irreversibly
degenerative CNS disease.
For more information, see the website of the National
Institutes of Neurological Disorders & Stroke:
http://www.ninds.nih.gov/disorders/parkinsons_disease
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