See also: PSP

The progressive paralysis supranucléaire (PSP), is also known as disease of Steele-Richardson-Olszewski . It was indeed identified like a Maladie with share whole, and thus specific to the beginning of the year 1960 by three Professors Neurologue S Steele, Richardson and Olszewski, which gave him their names.
Elle affects today several tens of thousands of people to the the United States and in Europe (40 to 60.000, according to the estimates). The PSP causes lesions of the cerebral Tronc gradually affecting the balance, the Vue, the Mobilité, the Déglutition and the Parole. The PSP remains however ignored and when she declares herself, she is still badly diagnosed with for consequence of the head ends often badly adapted. Thus, the majority of the patients reached of PSP report that them General doctor was unaware of very EC disease until the diagnosis is made by a neurologist and with the assistance of examinations by IRM.

A rare disease and orphan

The PSP can be difficult to recognize at the beginning because the initial disorders are also present in others neurodégénératives Maladies, like in particular those of Parkinson and Alzheimer. It is considered that the PSP accounts for 5 to 10% of the parkinson's syndromes. In the United States as in Europe where the disease is recognized now better, although remaining detected still often insufficiently well, one estimates at several tens of thousands the people who would be reached by it of each with dimensions of the Atlantic. Any disease is a disease of too but the PSP belongs to that where the number of people reached remains despite everything relatively weak, which makes a rare disease of it. It is there all the cruelty of this scarcity, because it is also in addition an orphan disease because to date no drug could show a therapeutic effectiveness proven in the treatment of the PSP. This absence of treatment specifically adapted to its pathology is, for the patient and his family, the source of many distresses.

Symptomatology

The earliest symptoms are a intellectual deceleration, modifications of the behavior which can appear in the form of a loss of interest for the ordinary day laborers activities or of an irritability and a susceptibility increasing. These behavioral disorders make think in a depressive state. Elocution changes, it also, with an impression of stammering, of nasal twang and difficulties of emitting comprehensible sentences. Thus these symptoms give a false impression of senility. But the most impressive symptom is the loss of balance to walk, person in charge of unexplained falls, the loss of balance worsens at the point to make walk difficult even impossible. To these disorders of mobility come to be added more insidious disorders such as visual difficulties. These visual problems result from an incapacity to correctly guide the eyes because of weakness or from the paralysis of the muscles which control the ocular spheres. Finally like the eye troubles, the disorders of swallowing belong to the later symptoms of the disease, those being able to involve " false routes " food.

Therapeutic prospects

The current treatments are primarily symptomatic and seek to fight against the embarrassment caused by the disease. For this reason the family and the entourage of the patient are essential, but they must themselves be constant and helped in this fight. Research aims to better including/understanding the mechanisms of the neuronal degeneration, in order to slow down the evolution of the disease. A payment on the orphan drugs was already adopted by the European Parliament since the December 15th 1999. European project NNIPPS, bearing on 800 patients proposed in 2001 studied specificities clinical, cognitive, neuro-radiological and histological of the PSP. The final results of this study are not published yet, but we alas know, to date, that the tests did not give the results of discounted effectiveness. Research is also carried out on the genetic bases or the nature of the disorders oculomoteurs and the balance which are characteristic of the affection. The hereditary factor is not the characterization of the disease. Finally of very many studies and research on the brain allow better and better to include/understand the complex mechanisms of its operation and its dysfunction. It is necessary to think that in the long term this work will lead to all the more interesting therapies as they will relate to a whole whole of neurodégénératives diseases and not only the PSP.

The protein TAU, a protein implied in the P.S.P.

The coding of proteins obeys biochemical and molecular mechanisms complex, with drawing to take up normal duties of life or dead (Apoptose) of our cells. The protein tau, as all the others is coded by our genes and any human being manufactures protein tau which is normally nonpathogenic. The gene coding the protein tau is located on chromosome 17.

The protein tau is a protein strongly expressed in the neurons and is located mainly in the axons. It is associated with the Microtubules and interacts with the microtubules via fields specific of connection to the microtubules and supports their assembly and their stability. The interaction of the protein tau with the microtubules is controlled by Phosphorylation. Tau is a phosphoprotéine which contains approximately 80 potential phosphorylation sites. The regulation of the phosphorylation state of the protein tau results from the joint activities of proteins kinases and proteins phosphatases. In general, a hyperphosphorylation of the protein tau decreases its affinity for the microtubules, which can involve their destabilization and consequently a disorganization of the Cytosquelette. However, a disturbance of the cytosquelette intervenes during the neuronal apoptose, indicating that modifications of the phosphorylation state of the protein tau could play a big role in neuronal death by apoptose. Very many diseases are related to disordered states of mechanisms which control the apoptose. Any anomaly of the apoptose can be responsible for release and the progression for many pathologies characterized by a deficit or contrary by an inappropriate activation to the mechanisms apoptotic. Thus, the apoptose could be implied in the neuronal death observed during neurodégénératives diseases such as the PSP.

The studies postmortem of brains of patients reached of PSP show the degeneration of the nervous cells of the brain in a certain number of zones where the presence of pathogenic protein tau is systematic. This presence is characterized by abnormal aggregates of this protein, without it being established to date, if they are the cause or the consequence of cellular death. The PSP is a tauopathy, which can be described as " pure" insofar as this disease seems to bring into play only one mechanism pathogenic related to the protein tau (or with its phosphorylation), which is not the case for example for the disease of Alzheimer, another tauopathy for which the protein tau also is very studied.

a hope : In the study of the University of Minnesota, carried out on mice, the researchers succeeded in controlling the production of the proteins tau in the brain of their guinea-pigs. By stimulating the production of proteins tau, the researchers succeeded in creating an insanity close to the disease of Alzheimer in the mice: their results with the tests of memory fell quickly. But when the researchers stopped the production of new proteins in the brain of the mice, not only the memory ceased worsening, but the performances with the tests started to improve. The brain of the mice was thus able to recover part of the ground which the proteins tau had made him lose. (Marion Garteiser, journalist health - 8/2/2005)

Of this only experiment, it is not possible to say today if such a result is reproducible at the human being. However this result is very encouraging, if it is considered that until the date of these experiments, confirmed by others since, it was held for irreversible the losses of intellectual abilities due to the neuro-degenerative diseases like that of Alzheimer, but also like that of the PSP.

Sources

• Association Progressive Supranucléaire Paralysis - PSP France