Paola Ximena Dalgo Aguilar is a research professor at the Universidad Técnica Particular de Loja and Coordinator of the research group on Non-communicable Chronic Diseases. She is working on the doctoral thesis entitled “Modulation of TNPO3 gene expression in LGMD1F limb-girdle muscular dystrophy” directed by Prof. Rubén Artero Allepuz and Dr. Ariadna Bargiela Schönbrunn from the Translational Genomics Group of the University of Valencia.
The main objective of her work is to advance in the characterization of the cellular model of myoblasts from patients with Limb-girdle Muscular Dystrophy 1F-D2 recently generated by the group of Prof. Juan Vilchez (Hospital La Fe). This characterization will serve as the basis for designing a targeted therapeutic strategy. The disease is caused by the presence of the mutant TNPO3 protein, which, as has already been shown, has a toxic effect in patients and in the disease models developed to date. Therefore, the strategies to be tested will be aimed at reducing the levels of the toxic protein thereby improving some of the symptoms of the patients.
Specifically, Paola Dalgo’s work will be based on designing antisense oligonucleotides that favor RNA degradation that subsequently gives rise to the mutant protein. Briefly explained, this type of strategy consists of designing a synthetic nucleic acid (containing DNA and RNA) that is capable of recognizing the RNA carrying the mutation. Once it is recognized, a molecule is generated that is capable of activating a degradation mechanism that decreases the levels of mutant RNA and that, as a consequence, decreases the levels of the mutant and toxic protein responsible for some of the symptoms that patients suffer from. patients. These types of therapies involve some technical challenges, including preventing synthetic antisense oligonucleotides from specifically recognizing mutant TNPO3 RNA and not other RNA sequences that are not related to disease in order to avoid nonspecific effects. On the other hand, it is also necessary to test various sequences that recognize different regions of the mutant RNA in order to identify those that are capable of triggering the reaction more powerfully in order to achieve the maximum possible reduction of the mutant RNA. It is important to highlight that antisense oligonucleotide-based therapies are currently on the rise, today there are around 12 drugs based on this strategy for the treatment of diseases such as Duchenne muscular dystrophy or spinal muscular atrophy. In addition, there are numerous ongoing clinical trials testing antisense oligonucleotide-based therapies, so it is expected that, in the coming years, their availability on the market will be greater.
We want to thank the research teams that form the medical alliance to find treatments against Limb-girdle Muscular Dystrophy 1F-D2 for their great involvement and always take into account all possible ways in the search for a cure and / or improvement for the patients.