Home Health Towards gene therapy for the most common muscular dystrophy

Towards gene therapy for the most common muscular dystrophy

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USE CRISPR-Cas9’s “cut and sew” gene editing system to correct myotonic dystrophy type 1 defect, the most common form of muscular dystrophy in adults. A group of Italian researchers attempting this path: the results of the preclinical study, that is based on cells derived from patients and on an animal model, have been published in the scientific journal Molecular Therapy Nucleic Acids, and are encouraging.

Rare diseases. Gene therapy works. This is what Crispr is

by Anna Lisa Bonfranceschi


Type 1 myotonic dystrophy

Type 1 myotonic dystrophy (DM1) affects the muscles and central nervous system, causing impaired heart function, muscle atrophy and impaired cognitive function. In the most severe forms, quality and life expectancy are severely compromised. The disease, which has the incidence of one case every 5000 individuals, depends on a genetic defect: the increase in the number of triplets of CTG (the cytosine, thymine and guanine bases, constitutive elements of DNA) present in the DMPK gene, which leads to a “toxic” messenger RNA for the cells. To date, there is no definitive therapy for this disease.

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I study

The new research, funded by the Telethon Foundation, was conducted by the Institute of Biochemistry and Cell Biology (Cnr-Ibbc), in collaboration with the Molecular Cardiology Unit of the IRCCS Policlinico San Donato of Milan and the San Donato Foundation Group. Scientists used the complex CRISPR-Cas9 enzyme system (which earned Emmanuelle Charpentier and Jennifer Doudna the 2020 Nobel Prize in Chemistry) to permanently eliminate the mutation. They used guide Rna, designed to position the Cas9 enzyme on the DNA sequences adjacent to the mutation to be removed, whose action can be regulated by administering an activating molecule. It is therefore a highly regulated system, which acts only for the time necessary to ‘cut the mutation’: a ‘timed’ therapy, therefore, to reduce the risk of possible complications in other genomic regions. “This technique allowed us to obtain an efficient correction of the genetic defect and of the molecular alterations typically associated with the disease”, explains Germana Falcone, coordinator of the study at the Institute of Biochemistry and Cell Biology of the National Research Council: “In the study we tested therapy on the tibial muscle and now we are trying to perfect it so that it acts on a systemic level, that is, to make it suitable for other muscles and all organs, including the heart. And in part we have already succeeded ”. The data obtained both in cultured cells derived from patients and in the skeletal muscle of mouse models (which contain a mutated human DMPK gene in their genome) confirmed that it is possible to correct the genetic defect in a modulable, safe and effective way. “It is therefore plausible – continues Falcone – that this gene therapy can be applied to patients suffering from the disease”.

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New therapies for genetic diseases on the horizon

Applied only recently in human cells for therapeutic purposes, the CRISPR-Cas9-based genomic editing method has produced results that bode well for the future of cures for various diseases. “With the appropriate modifications, the high efficiency and precision of this system can be exploited to make the technique particularly versatile”, concludes Fabio Martelli of the Molecular Cardiology Unit at the IRCCS Policlinico San Donato: “This means that it can be suitable for possible therapeutic applications in a large number of genetic diseases “.

Image credits: Warren Umoh on Unsplash

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