07 July 2011

Treatment of parkinsonism: dopamine neurons from fibroblasts

Dopamine defeated Parkinson's
Parkinson's disease is curable with the help of skin cellsAlexandra Borisova, Newspaper.


Parkinson's disease is one of the scourges of modern aging civilization. According to statistics, about one percent of all people over the age of 70 suffer from Parkinsonism in the world. The main manifestations of Parkinson's disease are slowness of movement, trembling of limbs, stiffness of muscles, instability of balance, depression, anxiety, irritability and indifference to others. This disease is associated with the death of special nerve cells – dopamine neurons. With the loss of 70-80% of these neurons, symptoms of parkinsonism occur: impaired movement, tremor (trembling in the extremities). In the future, patients lose the ability to make arbitrary movements: dopamine regulates motor activity. The most effective remedy for the treatment of Parkinson's disease today was created by an Austrian scientist of Ukrainian origin Oleh Hornikevich. In 1960, he first described dopamine deficiency in Parkinson's disease and in 1961 proved the effectiveness of treatment with a dopamine precursor, levodopa. Unfortunately, he never received the absolutely deserved Nobel Prize (together with Arvid Karlsson).

In general, dopamine, the "pleasure hormone", effectively regulates movement. Its low level in the body leads to impaired movement, while an increased level of dopamine causes hyperactivity, physical and mental arousal.

A group of scientists from Italy, among whom there are specialists of Russian origin, came close to the treatment of Parkinson's disease from the other side: instead of introducing dopamine into the body, they propose to make up for the deficiency of the cells that produce it – dopamine neurons – with the resources of the body itself. Their work is published by Nature (Caiazzo et al., Direct generation of functional dopaminergic neurons from mouse and human fibroblasts – VM).

Cell therapy – replacement of destroyed dopamine neurons in the brain of patients with "new" ones – is a very promising method of treatment. However, until now, the cultivation of neurons from the cells of the patient's own body was supposed to be carried out through the IPS stem cell stage, with induced pluripotency. The safety of their use raises big questions: starting to share indefinitely, they can give rise to a cancerous tumor.

The new approach involves obtaining dopamine neurons directly from connective tissue cells – fibroblasts. At the moment, the technology has been developed in cell culture. About the main results of the work of "Gazeta.Ru" said one of its authors, pharmacologist from the Italian Institute of Technology Raul Gainetdinov.

– Does your work really open the way to a complete treatment of Parkinsonism? That is, relatively speaking, in a few years, Mohammed Ali, a patient with Parkinsonism, will come to you, skin samples will be taken from him, neurons will be obtained from them, the implantation of which will lead to his complete cure from parkinsonism?

– Ideally, yes. But first you will need to work out the methodology on experimental animals. So far we have only received dopamine cells.

– Will such a patient need to constantly receive neurons, as diabetics need insulin?

– No, you don't need to. One procedure is enough to restore functions.

– What has been done in this particular work?

– My colleagues and I have learned how to grow neurons for Parkinsonism patients from their own skin. First it was done on mouse cells, and then on people with Parkinsonism.

– Tell us about the experiments carried out within the framework of the work.

– As you know, it is fundamentally possible to grow practically any type of cells from stem cells of human embryos. But there are serious problems associated with obtaining stem cells – the possibility of developing cancer and rejection of foreign tissue. Five years ago, a method was proposed for deprogramming fibroblasts to the stage of pluripotent stem cells, and then a new "programming" to the desired cell type. This is already a step forward: fibroblasts are easy to get from the patient himself – this is how the problem with rejection is solved. However, the problem with the possible induction of cancer remains. About a year ago, the possibility of reprogramming fibroblasts into another type of cell, bypassing the pluripotency stage, was shown. In this way, the problem of cancer is also solved. Work in this area is being carried out very actively: this year, glutamate neurons, blood cells, liver, and heart have already been grown using the proposed method. Recently, new articles have appeared almost every two weeks demonstrating the expansion of the method's capabilities (mainly Nature). Our group has worked out a method for obtaining dopamine neurons, which die in patients with parkinsonism.

– How long did the work last?

–Only about eight months. As I said, the topic is very "hot".

– Who led the research and where were they conducted?

– The main idea, work and merits belong to Vania Broccoli from the San Raffaele Scientific Institute in Milan, Italy. Three laboratories from the Italian Institute of Technology (IIT, Genoa), two of which are headed by Russian scientists – me and Alexander Dityatev, and the laboratories of the International School for Advanced Studies (SISSA) in Trieste and the Milan Parkinson Institute, also took part. Our Russian colleagues from IIT, Elena Dvoretskova and Tatiana Sotnikova, are also among the co–authors. All the others are Italians.

Portal "Eternal youth" http://vechnayamolodost.ru07.07.2011

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