The fight against low or very low prevalence diseases needs anonymous heroes and dedicated families. The encirclement of fatal family insomnia is a good example. Joaquín Castilla, a prestigious IKERbasque researcher at the CIC bioGUNE research center, exemplifies the selfless fight of many scientists against diseases as terrible as they are unknown. Miren Vitoria, a 27-year-old nurse, belongs to a family brutally beaten by this condition. Her paths have crossed in the fight against this neurodegenerative disease, with a greater presence in the Basque Country, which is characterized by affecting the part of the brain that controls the sleep cycle.
Joaquín Castilla is not only one of the main researchers on this and other prion diseases -the family to which fatal familial insomnia belongs-, but he is also the president of the Foundation that brings together those affected and their families. Actually, he has no family connection to this hereditary disease, although he does have a very strong professional and emotional connection. In 2013, after having worked in Switzerland and the United States as a university professor and researcher, he learned about a devastating case: a 12-year-old girl affected by fatal family insomnia and who died as a result of its effects.
This is the earliest case in the world in which a patient has developed this disease, a drama that would help to decant Castilla's involvement in this disease. The usual thing, in any case, is that carrier patients develop it around 50 or 55 years of age. The problems are triggered by abnormal production of prion proteins, faulty proteins that become infectious agents.
“Sleep control stops working properly because the neurons in the thalamus are dying. The name of the disease comes from that insomnia, which is often more of a non-refreshing sleep. It is one of the most characteristic manifestations of the disease. It occurs in almost all cases, although the symptom picture is much broader”, explains Castilla.
People who develop the disease also suffer from other conditions typical of neurodegenerative diseases: cognitive impairment, motor problems, dementia... Although there is also a characteristic of its own. “It is striking how quickly the disease develops. The deterioration is evident from week to week, and this occurs in a particular way with these prion diseases, unlike other neurodegenerative diseases that evolve more slowly. From the moment the first symptoms develop, the patients live between 6 and 18 months”, explains Joaquín Castilla.
The explanations of this researcher take on another aspect when Miren Vitoria recounts the terrible experiences of her family. In the last 25 years he has seen his grandfather, his great-uncle, his uncle and his aunt die from this disease. Last Christmas fatal familial insomnia reappeared in his family: his mother had begun to develop the disease. “In October she ran the Valencia half marathon. He finished it, though he realized it didn't come up to his usual mark. She started thinking about it, but she didn't tell us anything for a few months. His situation has gotten much worse since then, ”he explains.
Being a dominantly inherited disease, each descendant of a carrier person has a 50% chance of inheriting this genetic mutation. Many people claim the right not to know if they are carriers or not, at least until they decide to have children. “It is a point at which knowing it can change something, since through embryonic selection you can end the transmission from generation to generation. My brothers and I are clear that the suffering from this disease in this family will end us. We have suffered a lot”, says Miren Vitoria.
The Prion Diseases Foundation estimates that in Spain, one of the most affected areas of the world, there are currently around 200 carriers who will develop the disease at some point in their lives. Approximately half of them reside in the Basque Country: “The hypothesis is that this could have happened because a first patient who carried the mutation and who is called the founder, and whose origin could be from Eastern Europe, first migrated to Italy, to later settle in Álava where he had many offspring”.
Joaquín Castilla stresses that there are reasons for hope beyond the fruits that embryo selection can bring. Research centers in Spain, the United States and other European countries are working on promising therapies aimed at blocking the sudden destruction caused by prions. An American pharmaceutical company is also going to begin testing a drug that could change the living conditions of patients. It is the hope that families cling to that generation after generation have seen how insomnia became their worst nightmare.
