Gene therapy in the treatment of aromatic L -amino acid decarboxylase deficiency

Abstract

Aromatic L-amino acid decarboxylase deficiency is an autosomal recessive neurodevelopmental disorder caused by pathogenic variants of the DDC gene. The disease manifests already in newborns and infants. The presentation includes neurological symptoms, a significant delay in motor development and oculogyric crisis. Currently, gene therapy is successfully used in the treatment of aromatic L-amino acid decarboxylase deficiency. Until recently, no effective treatment for the disorder was known. The affected children died in the first decades of life. Gene therapy is a new and promising therapeutic strategy. The first genetic therapies for aromatic L-amino acid decarboxylase deficiency were implemented in the United States. The treated children recovered very quickly, began to sit up, stand, and even attempted to walk. For the first time in Europe, this method was used in 2019 in Poland, at the Interventional NeuroTherapy Centre at Bródno Hospital in Warsaw, with the involvement of a team of specialists under the leadership of Professor Mirosław Ząbek and Professor Krzysztof Bankiewicz. The therapy involves a real-time magnetic resonance imaging-guided introduction of a copy of the defective gene directly into the substantia nigra and the ventral tegmental area. Spectacular changes were observed in the first Polish patients treated with this innovative method. The children began to raise their heads soon after the procedure. Early accurate diagnosis and prompt implementation of appropriate treatment can minimise the consequences of deficient neurotransmitters in paediatric patients. This can be achieved with gene therapy, which is a chance for children affected by this rare disease.