Simone had her gene therapy. Today he “is fine and even more naughty than usual”, says her father just over a month after that delicate, innovative and long-awaited operation. In fact, Simone is only three years old but has been waiting for that therapy for two, to treat the rare degenerative genetic disease that affects his nervous system, the deficiency of AADC (decarboxylase of aromatic L-amino acids). A therapy that came after the appeal that the parents had made directly to the government to shorten the time. Yes, because that therapy had not yet been approved by the Italian Medicines Agency, and in order for it to reach the child, it was necessary to stir things up and streamline bureaucracy. The bumblebee is the first of 16 small Italian patients eligible to receive the therapy.
AADC deficiency: Simone’s story, waiting for gene therapy by Fabio Di Todaro 01 March 2023
The intervention at the Policlinico Umberto I, the first in Italy
To tell all this today, at the Policlinico Umberto I in Rome – first it is the only public hospital authorized at European level to administer the therapy – were the clinicians, family members, representatives of the institutions and of those who have told the story since from the beginning, such as the Observatory for rare diseases (Omar). At the Polyclinic last May 22 Simone received his therapy, thanks to the intervention conducted by Anthony Santorodirector of Neurosurgery, e Luke D’Angeloneurosurgeon of the Department of Neuroscience and Mental Health, and in the presence of Francesco Pisani, head of Child Neuropsychiatry at the Roman hospital. It took eight hours to safely inject the therapy directly into the child’s brain, thanks to the use of special cannulas capable of reaching the area of interest (the putamen) under magnetic resonance monitoring. Inside those cannulas, the long-awaited drug: eladocagene exuparvovec, a gene therapy consisting of a virus containing the gene for the production of the missing enzyme, necessary for the production of the neurotransmitter dopamine.
Gene therapy, 10 children without immune defenses treated by Letizia Gabaglio 21 December 2022
AADC, an ultra-rare disease affecting the nervous system
“AADC deficiency is a rare inherited autosomal recessive neurometabolic disease caused by mutations in the DDC gene,” he explained. Robert Battini, Head of the Clinical Department of Neurological Disorders and Rare Diseases, IRCCS Stella Maris Foundation of Calambrone (in the province of Pisa), who diagnosed Simone’s disease. Gene therapy against AADC aims precisely to reintroduce this missing gene (DDC, dopa decarboxylase gene) into the brain. “Clinical manifestations are generally evident in the first months of life and the most frequent include hypotonia, i.e. decreased muscle tone; hypokinesia, i.e. reduction or slowness of voluntary body movements; oculogyric crisis and autonomic nervous system dysfunction. In most cases AADC deficiency is severe, but some patients are known to have a milder disease course.” If it is true that the symptoms already appear in the very first months of life, it is also true that the diagnosis is often late, around 3 and a half years. Early diagnosis, with newborn screening, would now help to identify the sooner
disease and to intervene much earlier.
Locatelli: “The revolution of advanced therapies must be made accessible to patients” by Letizia Gabaglio 07 March 2023
In the severe form, Simone’s, children are unable to speak or walk, but the arrival of gene therapy eladocagene exuparvovec has changed the prospects of these patients, about 200 in the world. It must be said that from clinical studies some patients have not had motor improvements, while others have had significant improvements even in the short term. As happened to a Thai girl, she was among the first to receive therapy, after which she was able to run, swim, ride a horse. In fact, the therapy promises to help restore motor function, and also benefits cognitive abilities and language.
Thanks to gene therapy Rylae-Ann can walk by Fabio Di Todaro January 25, 2023
The appeal of Simone’s parents
“We are aware that Simone will not be able to recover 100%, but the results that emerge from the patients already treated give us hope that gene therapy could be the most effective solution for him at the moment too”, he told Salute only a few months ago Simone’s father. But in order for her to receive it, a collective effort was needed, which didn’t just involve clinicians. In fact, although the treatment was approved centrally by the European Medicines Agency, it had not yet completed its regulatory process in Italy. And for this reason Simone’s parents turned to the Prime Minister last March Giorgia Meloni and to the Undersecretary of State with Delegation for Rare Diseases Marcello Gemmato asking for help, because, they wrote: “I, my wife, and first our son we can no longer afford to waste time”.
Newborn screening: the example of Veneto and Tuscany for lysosomal storage diseases by Irma D’Aria 03 April 2023
The parents’ appeal was taken up by the institutions which, in collaboration with Aifa, the pharmaceutical company that produces the drug (PTC Therapeutics) and the clinicians set the machine in motion to ensure that Simone could receive her drug as soon as possible. And so it was. A lot of interventions were needed both on the regulatory level – with access to the Aifa National Fund for the use of drugs against serious diseases awaiting their marketing, as established by law 326/2003 – and on the clinical one, at the Umberto Polyclinic I in Rome, the only center in Italy equipped and authorized to administer the therapy.