Carola is a brilliant girl. High grades in school, a passion for fin swimming that she practices at a competitive level. Her full life as a teenager, she grew up in Fiumicino with Harry Potter books, the company of two brothers, the love of her parents Simona and Lorenzo. When the first seizure sets off an alarm bell, she is 13 and she is finishing middle school, with the prospect of attending high school. Suddenly her days become uphill. The crises are more and more frequent, the drugs begin to fail. And what was simple before is no longer simple: a math, walking, thinking. Putting the slow motion to her body and her mind is a very rare disease: Lafora’s disease.
A genetic alteration causes sugars to accumulate in particular in the brain, in the absence of the proteins that should synthesize them, involved in glycogen metabolism. It is a process that begins from birth, goes on for a long time in silence until the first symptoms. It messes up movements, weakens, deteriorates cognitive abilities, and it doesn’t stop. So much so that the life expectancy for these children is a few years, on average 5-10 from the onset of tangible disorders. For Carola, 2 and a half have already passed since the diagnosis arrived with the genetic examination, after an initial moment in which the disease was treated as juvenile myoclonic epilepsy. She is now 16 and continues to fight. Like her, about thirty patients are fighting in Italy, a country where there is a significant concentration of cases, if we consider that in the rest of the world there are at most a few hundred.
Few to attract funding or the interest of large pharmaceutical companies and create critical mass on the research front. Their hope hung on a promise of a drug using an RNA platform, which the American firm Ionis Pharmaceuticals had begun experimenting with. First in vitro tests, then on mouse models. “We were anxiously awaiting the coveted milestone of the start of the clinical trial on humans”, Carola’s uncle Alessandro Ippoliti told Adnkronos Salute. “A patient census had also started,” a very important study on the natural history of the disease documented in every aspect on about 30 patients. But something jams.
The dreams of the future of the Lafora children are broken on a few lines written by the company to communicate a postponement to a later date of the clinical phase: “Unfortunately, due to organizational constraints, in particular the human resources necessary to start a new clinical program, we are writing to inform you that the study is unlikely to start this year. We continue to explore potential alternative options. ”
“But we don’t give up – assures Simona Fochetti, Carola’s mother – We mainly have two possible paths and we ask for help so that at least one of them materializes”. The goal could be to bring research on this drug to Italy. “We ask that some company in our country come forward to give us a hand”, say both the uncle and the mother of Carola. “It seems that Ionis Pharmaceuticals is willing to grant the use of the patent – continues mother Simona – In practice, they tell the families to find a company that does the experimentation and this whole operation would cost, according to the intermediary company. , 10 million dollars “.
“It’s all very difficult – he unleashes – What can we parents do? Sorry, because the company had the protocol ready, already approved by the FDA. 20 children from all over the world would have been chosen for the experimentation, among those who are better off . Three centers involved, one in America, one in Spain, one in Italy “, the Bellaria hospital in Bologna. Now yet another stop. “But time runs fast for our children.” The American families of these patients, with the Chelsea’s Hope association, have pushed hard for the US government to finance research on this disease, explains Roberto Michelucci, director of the neurology unit of the Bellaria hospital – Irccs Institute of neurological sciences of Bologna. “And there has been a huge call for and funding from the National Institutes of Health (NIHs) and an effort by all the leading scientists in the field to understand the mechanism of the disease.”
Today, continues the specialist who has been studying the pathology for many years, “we know the responsible genes and the altered proteins, we know that there is a disturbance in the metabolism of glycogen, that glycogen has an alteration in its degradation so that it accumulates under form of these Lafora bodies within cells, causing their dysfunction and symptoms: epilepsy, muscle jerks, cognitive impairment, difficulty walking. The drug Ionis modulates the activity of an enzyme that produces glycogen, preventing more glycogen from accumulating. . In animal models we get the stop and a partial regression of the disease. There is very high evidence that the drug, which has also passed the toxicology tests in primates, can work “.
At the end of 2019, continues Michelucci, “it seemed imminent that we start with the clinical trial. Then there were delays. The company has many drugs for orphan diseases, at a certain moment it communicated that this was no longer a priority and they were trying to find a partnership with another company that could manage the transition to the clinic. The drug must be administered directly into the cerebral ventricles, because it does not pass the blood brain barrier. So a study requires a lot of funds, an important structure and skills. ”
This research on Lafora, continues the scientist, “had also produced two other drugs that serve to degrade and dissolve the bodies of Lafora, enzymes carried with monoclonal antibodies, very important, developed by Valerion that work in animal models, but the company it has not passed Covid and now a startup is starting that would like to carry them forward, but it takes money and partnerships. We are therefore in a phase in which the most promising drugs are on standby “. And therefore other faster available possibilities are also explored.
“For example – explains Michelucci – there would be a drug already approved and in use for Pompe disease”. It’s an enzyme replacement therapy, it’s called Myozyme *, it’s made by Sanofi. “The problem is that Pompe disease is a disease of the muscles and the heart, the Lafora of the brain. And this drug is not designed to cross the barrier between the blood and the brain. We hope it will partially pass, because in these people with epilepsy this barrier could be altered. The drug administered to the brain in the animal seems to work and talks have been started with Sanofi to ask for a compassionate study, but we still have no official answers. The Italian drug agency Aifa is also involved and will have to make its assessments “.
“We want a perspective – says Carola’s mother – Our children are aware of what is happening to them”, they see the tape rewind, they experience regressions and difficulties on their skin, “they ask us: why was I able before and now not? 24 months he does not leave the house waiting for this cure to arrive. We have held firm, but now we are in the phase of despair. They ask us for more time, but we do not have any. ”
It is precisely for this reason that one of the two associations that represent these patients in Italy is called ‘Tempo zero’. “It was born to try to raise awareness, raise funds and do something to save our children. We do not want more years to pass and it becomes too late”, concludes Simona. (Of Lucia Scopelliti)
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