Parkinson’s disease gene therapy tested in mice

US, WASHINGTON (NEWS OBSERVATORY) — During therapy, scientists tried to disable or completely remove the PTB protein from the genome of nerve cells, which “disables” the program for the formation of new neurons in the brain.

California molecular biologists have rid mice of an analogue of Parkinson’s disease with the help of gene therapy that blocks the work of a gene that interferes with the formation of new neurons in damaged areas of their brain. The article describing the study was published by the scientific journal Nature.

“For many decades, our colleagues have been unsuccessfully developing various methods for growing neurons suitable for experiments or to fight against neurodegenerative diseases using stem cells and other approaches. We were very surprised that we were able to grow so many nerve cells using such a simple technique,” ​​said one from the authors of the study, a biologist from the University of California at San Diego Xiangdong Fu.

Parkinson’s disease develops as a result of the destruction of the so-called black substance in the brain – a special department that generates dopamine, the hormone of pleasure, and directs it to the motor centers in the deep layers of the brain. The destruction of the black substance leads to the fact that a person begins to move poorly, cannot maintain balance and experiences pain when moving.

As is the case with many other neurodegenerative diseases, scientists still do not fully understand the nature of the development of Parkinson’s disease and do not know how it can be cured or at least stop its development. Existing drugs, such as levodopa or stimulants of dopamine receptor activity, can only suppress some of its symptoms in the early stages of development, and also have serious side effects.

Fu and his colleagues developed and tested the first experimental therapy that can inhibit the development of Parkinson’s disease. In the course of their study, they studied various genes that control the development and growth of nerve cells and various auxiliary brain bodies that nourish and protect neurons.

Turn off the brake light

All these cells are formed from the same “blanks”, however, after the birth of a person, the process of formation of new neurons almost completely stops, with the exception of the olfactory epithelium and some other regions of the brain. Scientists have long been trying to discover genes that play the role of a kind of “stop signal” for this process, but so far they have not been able to open them.

California biologists have found that in the case of neurons, the PTB gene and protein play this role. It interacts with certain types of RNA molecules, which are copies of genes, and prevents the cell from reading them. This “disables” the program for the formation of new neurons and other cells.

Fu and his colleagues have been trying for a long time to block the operation of PTB using short RNA molecules, but these experiments constantly ended with no result. After some time, scientists tried out an alternative strategy – they completely removed PTB from the genome of astrocytes, auxiliary brain cells, and did not temporarily disable it.

This led to the fact that almost all of these bodies turned into full-fledged neurons, capable of forming new connections with neighbors and replacing dead nerve cells. Based on this idea, biologists tried to cure Parkinson’s disease with the help of similar cells, experimenting on mice whose black substance was partially destroyed by toxins.

Scientists tried to repair her nerve cells using a virus that caused astrocytes to produce short DNA fragments that bind to RNA copies of the PTB gene and prevent cells from reading them. As subsequent observations showed, such gene therapy turned a small part of astrocytes into neurons, which led to an increase in the number of cells in the substantia nigra by 30% and the suppression of the characteristic symptoms of Parkinson’s disease.

According to the researchers, the mice remained healthy throughout the rest of their lives, which was not characteristic of rodents from the control group that lost a similar number of neurons from the substantia nigra. Fu and his colleagues hope that soon they will be able to begin clinical trials of this therapy to treat volunteers after they complete all experiments on mice and other animals.


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