Angelman syndrome, first tests in the world on therapy in Pisa

2023-11-07 15:39:41

An important milestone in medical research has been achieved in recent months with the launch of the phase 1 Halos trial, the first in the world aimed at evaluating the safety of the drug ION582, an antisense nucleotide (molecule used to prevent or alter the production of proteins) which should act in a targeted manner on the central nervous system, activating specific genes to improve the quality of life of patients with Angelman syndrome. This rare neurological genetic disease affects one child in every 15 thousand births in Europe, and is characterized by serious delays in cognitive development, neuromotor and sleep disorders, often drug-resistant epilepsy and absence of language. Those affected require chronic care, resulting in a significant burden on caregivers.

Thanks to the commitment of the researchers of the Irccs Stella Maris Foundation belonging to the Developmental Neurology Operational Unit directed by Roberta Battini, associate professor of Child Neuropsychiatry at the University of Pisa and Principal investigator of the trial, the Phase 1 Unit of the center of Clinical Pharmacology for drug testing of the University Hospital of Pisa welcomed for the first time a phase 1 trial (both on children and adults) which represents the first opportunity to experiment with the use of the antisense nucleotide in Europe where To date, 4 patients have been enrolled: the first 3 (2 children and 1 adult) in Pisa – the only center in Italy – and 1 in France. The United States, the United Kingdom, Australia and Israel are the other non-EU countries where the trial is being conducted.

In essence, in subjects affected by Angelman Syndrome, the maternal gene UBE3A (ubiquitin-protein ligase E3A) – the only gene functioning in the central nervous system of healthy individuals which, due to a complex biological mechanism called “imprinting”, guarantees regular development – is inactive due to a genetic alteration. Its absence prevents the regular maturation of the central nervous system. The experimental drug ION582, belonging to the category of second generation antisense nucleotides – to be administered directly into the spinal fluid of patients, is capable of activating the paternal gene (normally silenced by the imprinting mechanism) so as to make up for the absence of the mutated maternal one. This event is an important step in the scientific field, as the disease is still an orphan of specific therapies. “We are confident – declares Battini – that this drug can offer new hope for improving the quality of life of patients affected by the syndrome, although only the final results of this study, still in its early phase, and of the subsequent phases will be able to confirm its real therapeutic value ”.