Parkinson’s disease (PD) is a progressive neurodegenerative disorder consisting of the loss of dopamine neurons in a part of the brain called the black substance (Latin: the substantia nigra). As a result, the level of dopamine, a neurotransmitter that has a significant impact on the mood, is reduced. So far it has been thought that this is an incurable disease, like many brain diseases associated with the loss or impairment of nerve cells. Scientists continue their efforts to change this. It seems that we can witness the breakthrough that is awaited.
So far, most of the therapies have been focused on minimizing the effects of the disorder found. The aim was to save as many neurons as possible by protecting sensitive neural circuits. Growth factors were provided and reprogrammed cells were transplanted to save the existing ones or replace them. However, the effects were far from ideal.
The method of one-stage conversion of isolated mice’s and human’s astrocytes into functional neurons by depleting the RNA binding protein PTB (also known as PTBP1) aroused great hopes for effective treatment.
It sounds complicated but one by one.
The protein PTB has been looked at before. Its role was known and a way was sought to grow a cell line, constantly deprived of PTB. The results were not very satisfactory so far.
Finally, there was a breakthrough. In the first place researchers, they artificially caused Parkinson’s disease. A dopamine-like molecule was used to ‘poison’ dopamine neurons and cause their loss. In this way, mice developed symptoms similar to those expected from Parkinson’s disease.
In the following, a non-infectious virus containing an artificial piece of DNA had to be developed to specifically bind PTB-coding RNAs. It was degraded and could not act on functional protein. This stimulated neuronal growth.
Thus, we are talking about the use of antisense oligonucleotides, i.e. fragments of genomic DNA. They are used to inhibit the expression of genes. This method of use has been recently used in clinical trials, looking for effective ways to treat other neurodegenerative or neuromuscular disorders.
Then the antisensitive oligonucleotide PTB was applied to the mouse’s cerebrum.
The results turned out to be surprising. A 30% increase in the number of neurons was obtained thanks to the conversion of some astrocytes (stellar, largest glial cells) into them. However, this is not all. Dopamine levels returned to normal, and the neurons grew and seemed to function properly. After three months, the treated mice showed no symptoms of Parkinson’s disease and there was no relapse.
The therapy proved to be effective in mice. It was enough (as if it was so simple) to “turn off” PTB. Then we “turn on” the genes responsible for creating the neurons.
The results are extremely promising and certainly bring great hope to those suffering from this condition, also in an advanced state. What we have to remember is that we are talking about mouse testing. Testing on humans, on the other hand, should start soon. Let’s remember that when treating people, researchers are obliged to follow stricter standards than those of mice, so we must be patient.
1. Barker, R.A., Götz, M. & Parmar, M. New approaches for brain repair—from rescue to reprogramming. Nature 557, 329–334 (2018), https://doi.org/10.1038/s41586-018-0087-1
2. Qian, H., Kang, X., Hu, J. et al. Reversing a model of Parkinson’s disease with in situ converted nigral neurons. Nature 582, 550–556 (2020), https://doi.org/10.1038/s41586-020-2388-4
3. US San Diego Health Science, Heather Buschman, PhD, One-Time Treatment Generates New Neurons, Eliminates Parkinson’s Disease in Mice, https://health.ucsd.edu/news/releases/Pages/2020-06-24-One-Time-Treatment-Generates-New-Neurons-Eliminates-Parkinsons-Disease-in-Mice.aspx