Parkinson’s, a hope for a cure from stem cells that transform into dopaminergic neurons – time.news

2023-12-05 12:55:06

by Cesare Peccarisi

Danish study: eight days after implantation in mice with the disease, the lost motor functions were normally reactivated. Good results, but caution is still needed

Almost forty years have passed since, in 1987, Ignacio Madrazo of the Neurosurgical Department of the Hospital De Especialidades of Mexico City inaugurated in the New England of Medicine the technique of autologous transplantation of cells from the adrenal medulla into the cerebral caudate nucleus for the treatment of Parkinson’s disease, in two patients who did not respond to conventional pharmacological treatments. In fact, the adrenal medulla produces various hormones including dopamine, which is precisely the catecholamine that is missing in tremor disease, where the brain cells that produce it become ill.

Stamina cells

And it was he who, to improve the results of the first technique, inaugurated the transplant of embryonic stem cells from the fetal adrenal gland in 1991 in three other patients, with the aim of exploiting the potential of pluripotent cells and that is their ability to transform into any cell, including dopaminergic cells damaged in Parkinson’s. The idea, brilliant and revolutionary for its time, achieved only initially satisfactory results because the patients became ill again after a while.

Neurons from blood

In recent years, there have been numerous studies to identify the best stem cells for this disease and the one by La Jolla University cannot be forgotten, which made the cover of the Christmas issue of Science in 2000 with the title Turning blood into brain, that is, transforming blood into brain, where American researchers directed by Scott McKercher used the haematopoietic precursors of red and white blood cells from the bone marrow as a source to obtain neurons intended for patients with neurodegenerative diseases and lesions of the central nervous system. Ten years later, a study published in Cell by Rudolf Jaenisch of MIT indicated how to obtain pluripotent stem cells from peripheral blood which, despite being a rich and much more available source, once again did not provide stem cells suitable for obtaining the right neurons.

Stem compass

A possible solution has now arrived, with a study published in Nature Communication by Danish researchers at Aarhus University, directed by Mark Denham. The reason for the previous failures lay in not having sufficiently considered the infinite capabilities of these cells which, in the absence of a precise growth direction, can transform into practically any neuron and it is not certain that once implanted they generate precisely the ones needed. Danish researchers have just published the results of a research called DANDRITE, with which they managed to direct stem cells to transform into exactly the neurons they need.

Motor functions

Thanks to a sort of neuropharmacological compass developed in the laboratory, they have in fact engineered them into what they have called LRUSC stem cells, an acronym for lineage-restricted undifferentiated stem cells, i.e. undifferentiated stem cells with limited genesis which are strictly aimed at producing only and only the mesencephalic dopaminergic neurons that were missing. Eight days after implantation in the Parkinson’s mouse, the motor functions that had been lost were normally reactivated.

Japanese idea

With great intellectual honesty, the Danish authors admit that the milestone in this line of research belongs to the Japanese Shinya Yamanaka of Kyoto University who, in 2006, was the first to present on Cell genetic reprogramming based on four master genes, which can rejuvenate adult cells into embryonic cells, paving the way for the development of new stem strains and the biological mechanisms of cellular reprogramming that have now led to these results which, according to the authors, will soon have clinical application.

Caution

As captivating as it is, the result of the Danish colleagues must be taken with a pinch of salt for now – says Professor Alfredo Berardelli of the Sapienza University of Rome, past president of the Italian Society of Neurology and who has always been a point of reference for Parkinson’s disease -. The history of the last 40 years teaches us how the road that led to these pre-programmed stem cells is paved with discoveries and denials and we know that what works in mice is not always equally valid in humans. It could certainly be a turning point, because instead of fixing the damage downstream, we could act upstream, reprogramming the main primum movens of Parkinson’s disease. In the meantime, patients can still take advantage of the therapeutic and diagnostic progress made in recent years, which already today allows the disease to be identified earlier and therefore treatments with better results can be promptly instituted.

Alpha-synuclein

For the future, new treatments are looming, now being carefully evaluated, aimed at the anomalous protein alpha-synuclein which would also give rise to those alterations that the Danish stem cells aim to cure: being able to combine both of these therapies could be the final solution this disease.

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December 5, 2023 (changed December 5, 2023 | 11:35)

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