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 the New England of Medicine
the technique of autologous transplantation of cells from the adrenal medulla into the caudate nucleus of the brain 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 it in ’91 embryonic stem cell transplantation of the fetal adrenal gland 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 the dopaminergic ones 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 which made the cover of the Christmas issue of Science of 2000 with the title Turning blood into brain, that is transform blood into brain, where American researchers directed by Scott McKercher used the hematopoietic 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 on 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 said that once implanted they generate exactly what is 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 called LRUSC stem cells, an acronym for lineage-restricted undifferentiated stem cellsthat is undifferentiated stem cells with limited genesis which are strictly aimed at producing only and only i mesencephalic dopaminergic neurons that were missing. Eight days afterimplantation in the parkinsonian mousethe motor functions that were lost are 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 first, in 2006, presented on Cell genetic reprogramming based on four master genes, which can rejuvenate adult cells into embryonic cellspaving 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 grain 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 them 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 one 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
New treatments are emerging for the future, now under careful evaluation, targeted on the abnormal protein alpha-synuclein which would also initiate those alterations that the Danish stem cells aim to cure: being able to combine both of these therapies could be the final solution to this disease.
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December 5, 2023 (changed December 5, 2023 | 11:35)
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