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The Parkinson's disease story

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

Bibliography

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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