review
Bevorzugte PräsentationsartVortrag
TitelFirst stereotactic application of eladocagene exuparvovec into the putamen of a 3-year-old AADC-patient in Germany
Einleitung

Introduction: Aromatic L-amino acid decarboxylase deficiency (AADC) is a very rare autosomal-recessive inherited neurotransmitter disorder. In most cases it results in severe neurologic and vegetative impairments due to the impaired synthesis of dopamine and serotonin. The clinical effect of standard drug therapy consisting of dopamine agonists, monoamine oxidase inhibitors and vitamin B6 is still very limited. The intracerebral application of eladocagene exuparvovec, an adeno-associated virus-2 (AAV-2) based gene therapy, is the first causal therapeutic approach.

Patient/en und Methoden

Patient: We present clinical and biochemical data of a 3-year-old girl with AADC deficiency, who was treated as the first patient in Germany with an intracerebral application of eladocagene exuparvovec within the framework of an individual healing attempt.

Ergebnisse

Results: The patient was diagnosed at the age of 6 months. She presented a severe phenotype with striking muscular hypotonia, lack of head control, very limited spontaneous movements, recurrent oculogyric crises, no active speech, feeding and sleeping disorders, excessive salvation and sweating as well as nasal congestion. In September 2021 eladocagene exuparvovec was administered bilaterally into the putamen by stereotactic surgery. Postoperative MRI scans showed correct placement of the vector and no indication for any perioperative complications. Two weeks after the intervention the patient developed dystonia and uncontrolled movements, requiring the administration of midazolam despite the reduction of the standard medication (apart from vitamin B6). Regular monthly follow-ups revealed constant neurological progress. 4 months after application the child shows significant more and better coordinated spontaneous movements, has gained head control for 20 seconds, can lift the head in prone position and is more awake. Vegetative symptoms including sleeping disorders have improved while oculogyric crises and nasal congestion still appear nearly unchanged.

Schlussfolgerung/Diskussion

Discussion: The gene therapy vector was safely administered in our patient. Regular follow-ups document significant neurological improvements. Gene therapy might be a milestone in the treatment of AADC deficiency. Treatment response is age-dependent, emphasizing the need for early diagnosis. Approval of eladocagene exuparvovec in the European Union is expected during 2022.

review