Rare diseases, by definition, are rare. Therefore, even if its symptoms manifest themselves explicitly, it is always difficult to reach a diagnosis. Families know that something is happening; the doctors too; but no one is able to name it. That is what has happened to Aina’s parents, who has just turned five years old. At three months old, they noticed that something strange was happening to her little girl, but they didn’t get a diagnosis until she was three years old. The girl suffers from Irf2bpl syndrome, a neurodegenerative disease (which has no cure or treatment) that fundamentally affects the nervous system and leaves the majority of patients who suffer from it in a wheelchair before turning 10 years old.

A physiotherapist was the one who alerted Paola, Aina’s mother, about the early closure of her daughter’s fontanel – each of the membranous spaces in the skull before its complete ossification. The little girl was three months old at the time. They went to the doctor, who confirmed this. They also observed, and almost at the same time, that she also had a lot of stiffness in her neck and trunk. There she began the family’s ordeal until she found the diagnosis, which would arrive almost three years later: Irf2bpl.

They had finally managed to put a name to what was happening to their daughter. But the next steps to take were not very clear. “The doctors were just as lost as us,” Paola tells La Vanguardia. “It was they themselves – he continues – who advised us to look for other families with children with the same pathology. “They told us that by seeing what was happening to other older children, they could have some idea of ​​what would happen to my daughter.”

He regrets that “almost nothing is known about this pathology.” He explains that it is a “quite new” disease and that the first studies on it took place in 2016, when the first case appeared.

As far as we know, only seven children, including Aina, suffer from this mutation in the Irf2bpl gene in Spain (about 120 worldwide). She is the only case in Catalonia. There are two affected children in Madrid (Héctor and Martina); another in Burgos (Bilal); one in Granada (Elena); another in Murcia (Ahlam); and a last one in Albacete (Sergio). Since April, her families have formed the Spanish Association Irf2bpl.

Sergio – Paola says – is the smallest of all and the one who is the worst. Not only does she have epileptic seizures – she suffers them daily -, she also suffers from mobility problems – “she can’t move her arms, legs and trunk, nor her head because she has no strength,” explains Aina’s mother -, swallowing problems (she feeds herself through a tube) and breathing (many times you need oxygen to breathe). “By having a daily epileptic attack, the little progress he makes he loses the next day.”

Aina hasn’t had any, luckily. Her symptoms do not reach those extremes. In her case, she has a psychomotor delay. “She is 14 months below her biological age,” Paola argues. Now she should take P5, but she is repeating P4. She “is not at the level of a 5-year-old, but rather of a three-and-a-half-year-old.”

He just learned to speak about six months ago. “She vocalizes words, she can even say a phrase. He does not speak correctly, but he makes himself understood.” They perform periodic checks on the parts of the body in which the pathology affects: heart, digestive system, respiratory system, eyesight… “At the moment, it is quite stable.”

She moves around on her own, “although she is a little more clumsy than the others,” her mother emphasizes. “She falls quite a few times and runs differently than the rest, but she does it,” she adds. Winter is when she has it worst. She has many breathing problems and has to be admitted to the hospital two to three times.

Paola says that these children get worse over time as it is a neurodegenerative disease and that is why it is compared to ALS (Amyotrophic Lateral Sclerosis) or Alzheimer’s in children. “Little by little they lose all mobility, they stop being able to eat on their own… In many cases, in addition, it is difficult for them to breathe independently.”

Currently, and since June, there is research underway at the University of Murcia (UM) that aims to test hundreds of drugs, which are used for other diseases, to see if any could either reverse or stop the progression of the pathology. “If we were lucky enough that one worked, the fact that they are drugs that are already on the market would mean that they could reach the patient quickly: it is already approved, the doses, route of administration, toxicity are known…” explains Victoriano Mulero, professor of cell biology at the UM and responsible for the research.

He says that there are several teams of scientists, both in the US and Europe, currently working on this disease and that, in their case, they are using the zebrafish as a model (there are other researchers who work with the vinegar fly, for example). example). “The gene is highly conserved, which means that it is very important for life and all species have it,” he argues.

His idea is to explore two avenues. “One, remove the mutated gene to see what happens and, another, reproduce in the [zebrafish] model the mutations that each patient has to see if each one develops different alterations.”

For now, they have carried out the first one, which has already been successfully tested by some American researchers in the same model. They have removed the mutated gene in the larvae and have observed that alterations occur – which they can measure – in their movement.

He assures that they could now begin to test drugs (of those on the market for other pathologies) to see if there is one that reverses or reduces these alterations (they can test hundreds of drugs in a relatively short time).

The other approach is to reproduce the mutation of each patient. “But the first thing we need to see is if this second option is relevant, that is, if the fact of removing the gene is valid for everyone regardless of the mutation they have.”

What problem are researchers encountering? The usual. The foundership. Mulero confesses that they have had to use funds from other projects they work with to start this study. “It’s a drama,” he admits. Meanwhile, the Spanish Association Irf2bpl is trying to raise the necessary resources – they estimate around 50,000 euros – so that the investigation does not stop and can go to the end.