Myotonic dystrophy is a hereditary degenerative neuromuscular disease that occurs primarily in adults and affects approximately 50,000 people only in Spain.
Symptoms range from difficulty walking and myotonia (very difficult to relax contracted muscles) to severe neurological problems, unfortunately leading to progressive disability in many people in wheelchairs. The disease is highly heterogeneous among patients (age of onset, progression, hereditary transmission, affected muscle) and particularly complicates the development of generic therapies.
Currently, drugs for myotonic dystrophy are being developed in the following animal models: Drosophila, Fruit flies, or 2D cell culture. They will be tested later in mice and finally in patients. Unfortunately, some of the drugs developed using these approaches failed to reach the final stages of clinical trials because they were ineffective in patients, extrapolating the results obtained in animals to humans. I highlighted the difficulty of.
A team led by Javier Ramon, a professor of research at ICREA and head of the bioengineering group at IBEC, and Juan M. Fernandez, a postdoctoral researcher on his team, has created a three-dimensional model of myotonic dystrophy. I developed it for the first time. Uses bioengineering techniques and patient cells.
Part of the dissertation of IBEC researcher Xiomara Fernández, the study was recently published in the journal Biofabrication, paving the way for personalized and effective treatments for this rare disease and to date. there is no. This work is partially funded by a fundraising campaign launched by IBEC in late 2017-late 2019.
New 3D model of myotonic dystrophy:
Researchers started with fibroblasts in the patient’s skin. Fibroblasts are connective tissue cells that are involved in maintaining their structure and were previously “reprogrammed” into myoblasts, muscle progenitor cells. These myoblasts were placed in a matrix of gelatin and cellulose and the mixture was stamped with a kind of rubber to give it an elongated rectangular shape that simulated muscle fibers. The matrix was subsequently incubated under ideal conditions for myoblasts to continue their development.
What we are observing is that unlike classical cell cultures, the patient cells in our model fuse to adopt the 3D shape found in muscle and form the muscle fibers that are essential for its function. You can do it... “
Juan M. Fernandez, Researcher, Institute for Biological Engineering, Catalonia
Ability to test drugs in a personalized and fast way:
To evaluate the function of the new 3D model, researchers applied a drug called Antagomi R-23b to muscle fibers. The drug was previously developed by several authors of this study and, thanks to Arthex Biotech, will enter clinical trials in the not too distant future. They observed that both the molecular and structural characteristics of patient-derived fibers restore normal parameters during treatment and validate their use for the development of new drugs.
In addition, the model is low-cost, easy to implement, and faster than animal testing, accelerating the process of developing new therapies. This model represents a major step towards personalized medicine, as it is important to consider large patient-to-patient variability when looking for a cure for this disease.
“This new model allows patients to test different drugs and administer the drug with the best results in their cells. In this way, the treatment is personalized and more effective. No animal testing is needed, ”explains Xiomara. Fernandez, the first author of the article.
Fernandez-Gullivey, X. , et al.. (2021) Bioengineering In vitro A 3D model of myotonic dystrophy type 1 human skeletal muscle. Biofabrication.. doi.org/10.1088/1758-5090 / abf6ae..
New 3D model of myotonic dystrophy
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