Get SuperDani Stem Cells to Attack Mitchell Syndrome

A team from the Biomedical Research Center (CIBM) of the University of Granada is advancing in the Superdani Project, the first European study aimed at testing therapies against Mitchell syndrome, an ultra-rare neurodegenerative disease of which there are only 30 cases registered in the world, one of them, that of the Grenadian child Dani. 

On the eve of the concert of the Blues Band Granada to test different therapies on them. To this end, three different models are being generated: patient cell cultures, zebrafish and laboratory mice. 

For the development of the first model, in January of this year cells were extracted from the skin of little Dani, one and a half years old, cultured in the laboratory and transferred to the Biobank of the Health System Public of Andalusia, located in the same CIBM, in the PTS. “Last week we were told that they have already reprogrammed skin cells to stem cells. It is an important step because it is not possible to act directly on the patient and with the skin cells we have already done experiments and verified that they do not present the same alterations as the nervous system," says the specialist. 

The next step is to transform those stem cells into the two types of cells most damaged in Mitchell syndrome: neurons, which die progressively in these patients, and oligodendrocytes, responsible for the production of myelin, the fatty layer that covers nerve cells and the connections between them, whose deterioration produces the typical symptoms of disease. 

In Spain there are only two other patients with the syndrome, a man and his daughter in Murcia, and the CIBM team in Granada has samples from the adult for research. 

International collaboration 

In addition, it collaborates with the three research groups in the United States that are dedicated to this disease: one in Missouri, with a similar approach to production of nerve cells; another in Utah, with zebrafish; and a third in Texas, with the vinegar fly. 

The Utah group has sent zebrafish genetic material to Grenada, but the preparation is slow and complex. In the mouse model, it is the one that has made the least progress: first due to technical difficulties - Texan researchers have not yet managed to make a laboratory animal develop the disease - and secondly for economic reasons: "A new mouse model of this disease can cost 30,000 or 40,000 euros". 

“Stem cell experiments are also extremely expensive - they need a growth media specific to the type of cells we want. On each small plate in the laboratory there are thousands of euros," recalls Ranea, who highlights that with the 100,000 euros already raised by the project, the first part of the research is guaranteed. 

Already approved drugs 

Researcher Ramón y Cajal of the UGR's Department of Physiology clarifies that, within the framework of the SuperDani project, therapies already available will be tested to study whether they produce changes in the different experimental models. “We're not going to blind. We rely on drugs already approved by the European Medicines Agency and the US FDA that are effective in neurodegenerative diseases that also affect myelin, such as leukodystrophy or multiple sclerosis, especially antioxidant and myelinating drugs. ”

This way, remember, the process is much faster because you don't have to test a compound chemical from the start, with years of clinical trials and safety testing. Especially, he points out, when the patient is a child and the disease, although very variable from one patient to another, progresses very quickly. The average life expectancy is between five and ten years. “Every case is a world,” the researcher acknowledges. 

The terrible symptoms of a disease without care

Mitchell syndrome is a progressive neurological disorder caused by a spontaneous mutation in the ACOX1 gene that alters the functioning of peroxisomes, the structures of cells responsible for breaking down fats. By working in an uncontrolled way, they destroy the cells that generate the protective layer of myelin around the nerves and alter the transmission of nerve impulses from the brain to the body. Symptoms include loss of muscle strength and mobility, hearing loss and vision problems, skin rashes, cognitive impairment, and airway involvement. 

Source: IDEAL