It's called Mtf1 and it's a new possible therapeutic target against Huntington's disease (or Huntington's chorea). In fact, tests conducted in vitro and in animal models show that, by modulating its expression, it is also possible to counteract the effects of the disease. An interesting discovery for Huntington's disease, still without treatment. The results of the preliminary research, conducted at the University of Padua and financed by the Telethon and Armenise-Harvard Foundations, have been published in Nature Communication.
Huntington's disease, hunting for protective genes
Huntington's disease is a neurodegenerative disease of genetic origin: a mutation of the IT-15 gene causes the accumulation of the diseased protein known as huntingtin, which poisons the nervous system, causing neuron death. But, wondered the Paduan team, are there mechanisms capable of suppressing this toxicity? In detail, are there any genes that could protect against Huntington's disease? "Starting from the general concept that all our cells have protective mechanisms against various forms of stress, we focused our attention on some genes to evaluate their 'protective' function against Huntington's disease", he explains Gratian Martellthe lead researcher of the study and head of the pluripotent stem cell laboratory at the University of Padua.
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Mtf 1, the new possible therapeutic target
To understand this, the researchers carried out a genetic screening on mouse stem cells that expressed the mutant huntingtin protein. "We identified one, called Mtf1, which demonstrated this protective ability in several models of Huntington's disease, such as zebrafish or mice, in which the same genetic mutation responsible for the disease in humans had been introduced," they explain. Giorgia Ferlazzo And Anna Gambettarespectively first and second author of the study.
In fact, the article reads, the forced expression of the Mtf1 gene is able to counteract cell death, the formation of protein aggregates and oxidative stress in mice, effects caused by the accumulation of the mutated form of huntingtin and responsible for the symptoms of the disease, including motor defects. The same strategy leads to the reduction of malformations and programmed cell death (called apoptosis) in zebrafish. These results were then confirmed in a "human" model, he explains Sonya Amato, co-author of the study, “that is, in diseased neuronal cells obtained from human stem cells obtained from a sample donated by a patient. Also in this case Mtf1 proved to be able to reduce some of the characteristic defects of Huntington's disease: an encouraging result, which pushes us to continue on this path to develop a new therapeutic strategy in the future".
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The next steps
In animal models, explains the researcher, viral vectors or mRNA sequences were used in order to force the expression of the Mtf1 gene, and it is not yet clear how the result could be replicated in humans, Martello concludes, adding: "We have already patented our discovery and now we intend to found a start-up with the sole mission of transforming these scientific discoveries into a new therapeutic approach, thus bridging the gap that exists between university research and industrial development".