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Back to 2020-02-29-Opinión-CIMA-Enfermedades raras
Dr. Cristian Smerdou, director of the Gene Therapy and Regulation of Gene Expression Program of Cima University of Navarra
Rare diseases: making research a reality
While gene therapy is already effective against some of these diseases, research is advancing in the search for treatments with other techniques such as editing Genetics or the use of new therapeutic molecules.
Rare diseases are those that affect approximately 5 out of every 10,000 inhabitants. Worldwide, nearly 7,000 rare diseases have been identified, pathologies of a chronic and degenerative nature, most of which are genetic in origin. It is currently estimated that between 6% and 8% of the population in Europe suffer from them, i.e. between 27 and 36 million people. In Spain, more than 3 million people are affected, more than half of them being children.
The complexity of identifying these diseases and their low prevalence make diagnosis difficult, and it can take several years to "name" the disease and find the appropriate treatment, which in many cases either does not exist or the therapeutic alternative is palliative rather than curative. However, the research, hand in hand with technological advances and development of new techniques, is already offering answers to some of them.
One example is the innovation in the field of gene therapy, a technique that seeks to cure a disease caused by the lack or dysfunction of a gene by replacing it with its correct version. To achieve this "restitution Genetics" it is necessary to deliver the correct information Genetics to the patient's cells. To do this, vehicles or vectors are used, generally viruses modified in the laboratory that lose their capacity to cause disease but maintain their skill to penetrate the cells, introducing the correct information Genetics . Thanks to design and the implementation of these vehicles, at Cima of the University of Navarra we designed a new treatment capable of curing Wilson's syndrome in an animal model . This pathology is a disease that affects one in 30,000 people and is caused by the mutation of a gene responsible for the metabolism of copper, causing this metal to accumulate in the liver and other tissues causing liver and neurological damage, which can lead to death. The treatment originated at Cima is based on a viral vector, called VTX801, which is currently at development by the business biotechnology company Vivet Therapeutics (whose 15% of the company belongs to the multinational pharmaceutical company Pfizer) and will soon start a clinical trial at essay .
Another therapeutic alternative at development is editing Genetics. Researchers at Cima have also demonstrated in animal models that, using CRISPR/Cas9 technology, a technique that allows us to "edit" or "correct" DNA, we can stop the development of primary hyperoxaluria, another rare liver disease caused by a mutation in a gene that causes the accumulation of a toxic substance called oxalate in the kidney. In this case, the researchers used CRISPR/Cas9 technology to block that mutated gene, preventing the accumulation of oxalate, which reversed the disease in the animals. Further progress in this area research could make it possible in the future to treat patients before they lose kidney function, thus avoiding the need for transplantation.
Other research is also underway that, instead of targeting the DNA of genes, focuses on other molecules such as RNAs, which function as messengers of information Genetics within cells. Specifically, researchers at Cima have developed a technology based on introducing into liver cells an RNA capable of correcting the symptoms of acute intermittent porphyria in animal models. This rare disease is also Genetics and is caused by the liver's inability to metabolize compounds needed to produce hemoglobin (a specific blood protein). This causes these compounds to accumulate in the blood causing toxicity. It presents in the form of painful intermittent crises and can lead to significant neurological damage and even require liver transplantation. In these patients the crises can be triggered by certain medications, strict diets or prolonged stress. However, the main triggering factor is the female hormones associated with the menstrual cycle, which is why it occurs especially in young women with important work and family responsibilities.
For other rare inherited diseases, research is already a therapeutic reality. Currently, there are seven gene therapy products approved by American and European regulatory agencies and health authorities for clinical use. These treatments are aimed at treating beta thalassemia (blood pathology caused by the lack of a gene involved in hemoglobin training ), spinal muscular atrophy (caused by the lack of motor neurons), Leber's congenital retinal amaurosis (caused by a mutation Genetics that prevents the production of a protein essential for normal vision) and adenosine deaminase deficiency (mutation Genetics that prevents lymphocytes from being present in the blood).
These programs of study are examples of how research, thanks to technological progress and scientific innovation, is getting closer to providing solutions for patients with these diseases. However, in order to ensure that more treatments will soon become a therapeutic reality, it is essential to continue the support, both social and institutional, in promoting research, since in order to reach the clinic it is necessary to start at laboratory.