Our movements are partly ordered by a
biochemical substance, the dopamine, secreted by
specialized cells located in a center located in
the base of the brain (a black substance, also
called locus niger).
When these cells are destroyed, they do not
secrete dopamine anymore; the:
musculature solidifies and is prone to shakings.
Syndromes of Parkinson’s
Cells secreting of dopamine can be destroyed in
various ways.
Certain cases have a genetic cause, several
active genes having been identified in families
of those with Parkinson’s.
Other cases are caused by the exposure to the
pesticides.
The
Frozen Drug Addicts
(1)
When
William Langston, a neurologist at Santa Clara
Valley Medical Centers
in the Northern of California, was stunned
to see when he sees arriving at his consultation
a motionless young man, as frozen, mute, and his
open, large eyes without eyelids' unblinking.
One
also understands the stupefaction of the other
doctors who did never saw such a case before.
By
examining the friend of the young man, Langston
and his fellow neurologist, Phil Ballard, noted
that she was in the same frozen state
as him.
They
suspected a connection between the two cases.
By
chance, Phil Ballard went to a meeting arranged
by one of his neurologist friends, James Tetrud,
who told him he’d to have seen two similar cases
in his consultation.
The
four-frozen people were heroin addicts.
Langston went on television to alert the
community of the existence of a bad heroin sold
in the street.
Following this emission, a spectator announced
two other cases.
Six were frozen.
Langston got remaining samples of the powders
that the victims had injected.
Analyses of the powder sold as heroin showed in
fact that it was a toxic synthetic product,
the MPTP.
The MPTP
(MPTP:
1-methyle,
4 -
phenyl,
1-, 2-, 3-, 6-tétrahydro
pyridine),
is
a
neurotoxin
that
causes the permanent symptoms of the
Parkinson’s disease
by
destroying certain
neurons
in the
black
substance
of the
brain.
It is used to study the disease in monkeys.
The story of the frozen drug addicts was told
with passion by William Langston and Jon
Palfreman, a medical writer, in a book called
The Case of the Frozen Addicts:
How
the Solution of an Extraordinary Medical Mystery
Has Spawned a Revolution in the Understanding
and Treatment of Parkinson’s Disease
(1).
The neurotoxicity of the MPTP had already been
suspected in 1976, when Barry Kidston, a
twenty-three-year-old student of chemistry in
Maryland,
had injected himself with a drug that he had
synthesized in an incorrect way. He had been
contaminated by the MPTP, and, after three days,
he had developed the symptoms of the Parkinson’s
disease.
The Parkinson’s syndrome of Kidston had been
treated successfully with Levo- dopa,
but he died eighteen months later from a cocaine
overdose. At the time of autopsy, they
discovered the destruction of the dopamine
receptors of the black substance.
The Parkinson’s Disease
It is a
degenerative chronic neurological disease
(progressive loss of the neurons) affecting the
central nervous system.
It is caused
by an
insufficiency of production of dopamine in the
brain.
When the cells that secrete the dopamine die or
are damaged, one sees the appearance of motor
disorders of progressive evolution.
The Parkinson’s
disease usually begins at forty-five (ages for
the beginning of andropause disease) or after.
It is the second
most frequent neuro-degenerative disease, after
the
Alzheimer’s disease.
The Parkinson’s
disease is distinguished from the
Parkinson’s syndromes,
which are generally of various origins (genetic,
exposure to the pesticides), are more severe,
and which respond little to treatments.
Symptoms of the Parkinson’s Disease:
Motor symptoms:
shakings, muscular rigidity, slowness of
movements, losing
balance.
Non-motor symptoms :
constipation, disturbed sleep, emergencies to
urinate, frigidity, impotence, dizzy spells,
tiredness, depression, memory disorders.
Treatment of the Parkinson’s Disease
There doesn’t yet exist yet any curative
treatment for the Parkinson’s disease.
Substitution of the
Dopamine:
The Parkinson’s disease is due to an
insufficiency of production of dopamine. The
drugs making it possible to treat it mitigate
this insufficiency either by giving dopamine
(L-dopa), or by providing an agonist of the
dopamine (molecule miming the action of the
dopamine). These various classes of drugs
constitute today, for a great majority of
Parkinson’s sufferers, the
central element of the treatment.
The L-dopa is the most powerful drug for the
improvement of motor disorders.
Inhibiters of the Mono Amine Oxidase
The inhibiters of the mono amine oxidase ( IMAO)
are molecules that block the enzyme degrading
the dopamine.
They
can be used only at the beginning of the
disease, or to prolong the effects of the
L-dopa.
Unfortunately, the association of the IMAO with
certain drugs is risked, in particular
antidepressants often prescribed, like the
fluoxetine (Prozac).
An old publication going back to 1974 attracts
our attention here.
It is a clinical study evaluating the action of
testosterone on the activity of the monoamine
oxidase in seven depressed men.
|
Average activity of MAO (monoamine
oxidase) in plasma
|
|
Before treatment
|
7223 ± 3740
|
|
After treatment
|
1997 ± 1250 (p<0,01)
|
|
400 mg. of testosterone cipionate every
twenty-one days
|
According
to Klaiber and collaborators.
The conclusion of this study is that :
Testosterone, in sufficient quantity, naturally
lowers the quantity of MAO (Mono Amine Oxidase),
thus preventing the degradation of the
production of dopamine (2).
From where the interest to study of the
daily
androgens'
production in men suffering from a Parkinson’s
disease, with the aim
losing balance.in
order to
save
their dopamine production.
By the same token, taking occasion the take of
androgens will decrease the tendency toward
nervous
breakdowns (and will limit the taking “ of
antidepressants”.
The destruction of cerebral cells producing
dopamine causes the symptoms of the Parkinson’s
disease.
That was shown with precision by the study of
the frozen drug addicts, whose cases are
extremely rare.
What is the cause of dopamine cells’ destruction
in those with Parkinson’s one whose symptoms
usually
begin
between forty-five and seventy years old?
The health of those with Parkinson’s depends on
an aging disease that strikes the whole of the
organism after forty years and sometimes even
before:
the andropause disease (chapter 1).
Diseases
of aging develop in a permanent vascular
disorder caused by
arteriosclerosis, atheroma, and arterial
hypertension
The very small arteries that
constitute the end of the arterial network are
particularly vulnerable.
They
are the first to be blocked by a lack of
androgens hormones.
Their
obstruction deprives the cells of oxygen,
causing their destruction.
Contributions of essential molecules like
androgens, necessary to the survival of these
cells, are also compromised.
The
cells that produce the dopamine, localized in
the depth of the brain, are located at the end
of the arterial network.
It
would not be astonishing that one of the causes
of the destruction of the cells producing
dopamine resides in the fact that they are not
irrigated anymore normally by blood anymore
since the final arterial network,
extremely fine, can be blocked.
The testosterone could play a producing,
determining role on biochemistry, even of the
cells producing dopamine or by improving blood
circulation on the level of these cells.
|
Normal production
of
androgens
|
Insufficient production of androgens
|
|
↓
|
↓
|
|
Very small,
permeable arteries
|
Very small,
blocked arteries
|
|
↓
|
↓
|
|
Normal
dopaminergic cells
|
Dopaminergic
cells
destroyed
|
|
↓
|
↓
|
|
Normal production
of
dopamine
|
Insufficient
production of dopamine
|
|
↓
|
↓
|
|
Normal movements
|
Shakings
|
Exceptional Treatment
Surgical treatment
(major cerebral stimulation or SCP) or
graft reprogrammed stem cells
are the focus of the medical research.
Stem
Cells
The
National Institute of Neurological Disorders and
Stroke
(NINDS) in the United States supports
research on stem cells biology, in the
development of the adult brain, and in studies
of spinal-cord lesions.
Studies are also made on the possibility of
producing dopamine by stem cells.
Growth Factor FGF20
In
2013,
Nobuyuki Itoh and
Hiroya
Ohta of the Department of Genetic Biochemistry,
Kyoto University Graduate School of
Pharmaceutical Sciences, in Kyoto, Japan, showed
the importance of growth factor FGF20 in the
differentiation of the stem cells in cells
producing of the dopamine (3).
The use of the stem cells to treat the
neurological diseases in man is very promising.
There remains, however, much work to do before
being able to apply this therapeutic treatment
in private clinics.
To carry out these future treatments quite
successfully,
general aging of organism's structures
will always be taken into account
B ibliography
1.
Langston W., PALFREMAN J. The Case of the
Frozen Addicts: How the Solution of an
Extraordinary Medical Mystery Spawned a
Revolution in the Understanding and Treatment of
Parkinson's disease.
Pantheon Books, New York, 1995.
2. KLAIBER E.L., BROVERMAN D.M., VOGEL W.,
KOBAYASHI Y. The use of steroid hormones in
depression. In Psychotropic action of hormones.
Proceedings of the World Congress of biological
psychiatry. Buenos Aires. Argentina, September
1974. Spectrum publications INC.
3.
NOBUYUKI ITOH
and
HIROYA OHTA.
Roles of FGF20 in
dopaminergic neurons and Parkinson's disease.
Frontiers in Molecular Neuroscience;
www.frontiersin.org. Volume 61 Article
15: 1-4.
May 2013
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