AADC deficiency: Simone’s story, waiting for gene therapy

His name is Simone, he has just turned three and he is one of 10-15 Italians to suffer from aromatic L-amino acid decarboxylase deficiency (AADC), an ultra rare metabolic disease. The severity of his illness is considered compatible with the possible administration of the gene therapy, eladocagene exuparvovec, via an infusion directly into the brain. However, the lack of approval by the Italian Medicines Agency (Aifa) is freezing the hopes of the parents. “We are waiting for news in the coming months, otherwise we will try to go abroad”, father Sebastiano and mother Sabrina explain to Salute.

Waiting for AIFA approval

In San Giovanni La Punta, a municipality on the slopes of Etna, the life of this family flows in anticipation of news from Rome. More precisely from via del Tritone, headquarters of Aifa. After the go-ahead for the administration of this innovative gene therapy by the European Medicines Agency (EMA), the go-ahead from the Italian one is needed to “try to give Simone a better life”, says Sebastiano. The coveted solution lies precisely in the possibility of administering gene therapy. A hypothesis also supported by the doctors who are treating him between the Irccs Stella Maris Foundation and the Umberto I Polyclinic in Rome. Simone received the diagnosis in the first facility, while the hospital in the capital is currently the only one in Italy authorized to treat patients suffering from AADC deficiency with gene therapy. It is from here that Vincenzo Leuzzi, director of the complex operational unit of child neuropsychiatry, sent the request to AIFA to access the so-called 5% fund: a treasure trove through which, since 2003, it is possible to request coverage of the necessary expenses guarantee therapies for which there are preliminary efficacy data to people suffering from a rare disease. “The answer was negative, so now all that remains is to wait for the ordinary procedure to be completed with the approval of the treatment, which will follow the approval already given by the EMA”, says the specialist. Alternatively, an attempt could be made to ask the company (PTC Therapeutics) for the ok to grant the drug for compassionate administration, ie outside of a clinical trial, as is already the case in France and Germany.

AADC Deficiency: What Is It?

The disease from which Simone suffers is characterized by the deficiency of an enzyme without which the body is unable to synthesize the neurotransmitters dopamine and serotonin. Impaired synthesis of these mediators reduces brain connectivity. Hence the onset of a series of neurological and non-neurological symptoms: from movement disorders to intellectual disability, from nasal congestion to the appearance of respiratory and digestive system disorders. “Already in the first six months we realized that something was probably not going in the right direction – says Sebastiano -. Muscle tone was greatly reduced throughout the body. And, over the months, more serious symptoms have been added, such as eye deviations (oculogyric crises, ed.) and moments of enchantment and reduced attention. The months went by, but Simone appeared much smaller than his age”. Getting the expected answers was not easy, as often happens when dealing with very rare diseases. After a long wandering in Sicily, the answers came from Pisa. “But I don’t blame anyone, we are aware of the difficulty of completing a diagnosis of this type and of its exceptional nature”, admits Sebastiano.

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A life of sacrifices and hopes

Meanwhile, the life of Simone and her family flows with many sacrifices. “Our son doesn’t walk, but he moves while sitting and dragging himself on his arms – says his father -. In addition, he does not speak, suffers from a very strong sialorrhea (intense salivation, ed) and oculogyric crisis (spasm of the oculomotor muscles that block the eyeballs in a fixed direction, usually upwards, ed). In this period he also underwent two operations to remedy a dislocated hip, which we do not yet know if it could have occurred as a consequence of his illness. Our life, but especially Simone’s, is quite complicated. He takes medicines and supplements every day, undergoes physiotherapy three times a week and periodically undergoes speech therapy. His hope is to be able to offer him as soon as possible the opportunity to regain independence and grow in a dignified manner. We are aware that Simone will not be able to recover 100%, but the results emerging from the patients already treated give us hope that gene therapy could be the most effective solution for him at the moment”.

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