Replacing neurons lost due to neuro-degenerative disease is a goal that neuro-scientists around the world have been working on for some time, without however being able to achieve truly satisfactory results. Now, however, a study published in Nature seems to mark a turning point: scientists from the University of California San Diego have managed to convert – unexpectedly, they admit – astrocytes (a type of glia cell, the neuronal support tissue) into neurons that produce dopamine in the brains of mice with Parkinson’s disease, and the animal symptoms are disappearing.
The Parkinson’s disease is a clinical condition due to the death of neurons that produce the neurotransmitter dopamine in an area of the brain called the substantia nigra. When about 80% of these neurons are lost, symptoms occur: tremors, slow movements, stiffness, etc. Medical science to date manages to relieve symptoms, sometimes to slow the progression of the disease but healing is not possible.
One way to cure is to replace dead neurons and someone has tried transplanting stem cells, but the results are limited: neurons, when and if they take root, do not establish connections. The most promising alternative would therefore be to understand if and how it is possible to convert other brain cell types into neurons.
The turning point
By studying this eventuality, the Xiang-Dong Fu team of the University of California San Diego focused on the Ptb protein , which is able to modulate the expression of genes in different types of cells, from fibroblasts, which are common cells. connective tissue, to astrocytes, which are resident cells of nerve tissue.
The researchers tried to silence Ptb protein in astrocytes (both murine and human) in vitro and after a few days they observed a conversion of these cells into neurons. “The fact that we managed to produce so many neurons in a relatively simple way,“ commented Fu, “was a great surprise.“
The next step was to verify whether such a conversion replicated in vivo in mice. Scientists have thus tested the new approach on an animal model of Parkinson’s disease, showing that even here astrocytes transform into neurons that produce dopamine and even establish connections with the rest of the brain. And, unexpectedly, the motor symptoms of the disease subside .
A step at a time
It must be said that the Californian team is not the only one to have attempted this approach. A very similar strategy was adopted by the group coordinated by Hui Yang in Shanghai and led to similar results regarding the conversion into neurons, published on Cell last April.
Success, therefore, does not seem to be accidental. But even if the enthusiasm is legitimate, it is advisable to proceed with lead feet before talking about a short-term clinical trial .
As pointed out by the authors themselves, there are several aspects to be investigated again and an efficiency problem to be solved.
First of all, it is necessary to deepen the safety of the techniques used to silence the Ptb protein and promote conversion. Can they be applicable in humans ? Could they create collateral damage in other cells of the body? And again, what could the exhaustion of the astrocyte population entail ?
Then, it is still not clear how astrocytes convert into the right type of neurons , the ones that produce dopamine. One hypothesis is that, once the brake of the Ptb protein is removed, they are conditioned by the surrounding environment . If this were the case, it would be better to understand more: identifying local and specific factors could be the key to improve the efficiency of the conversion from astrocytes to neurons (which at the moment is not particularly high), improve the quality of the converted cells and avoid creating cells unwanted.