Future Focus

First diseasemodifying treatment for AADC deficiency

The EC has approved the first gene therapy directly infused into the brain
The European Commission (EC) has granted a marketing authorisation for Upstaza (eladocagene exuparvovec), the world’s first disease-modifying treatment for aromatic L-amino acid decarboxylase (AADC) deficiency.
Upstaza is additionally the first marketed gene therapy directly infused into the brain.
The treatment, formerly known as PTC-AADC, has been approved for patients 18 months and older.
“Today’s approval from the EC for Upstaza, for the treatment of AADC deficiency, is momentous for patients, for PTC, as well as for the larger gene therapy community,” commented Stuart W Peltz, PhD, CEO, PTC Therapeutics. “We are proud to bring this innovative therapy to the marketplace so that patients may benefit. Upstaza is the first and only approved disease-modifying treatment for patients living with AADC deficiency. We are ready to deliver this long-awaited treatment to patients as soon as possible.”
The approval is based on several clinical studies, in which patients went from not achieving any developmental motor milestones, to demonstrating clinically meaningful skills, from as early as three months following treatment. Transformational improvements were shown to continue up to ten years after treatment.
AADC deficiency is a very rare, fatal genetic disorder that typically causes severe disability and suffering from the first months of life, with many impacts – physical, mental, and behavioural. The suffering of children with AADC deficiency may be exacerbated by episodes of distressing seizurelike oculogyric crises, causing the eyes to roll up in the head, frequent vomiting, behavioural problems, and difficulty sleeping.
The disorder is characterised by decreased activity of aromatic I-amino acid decarboxylase, an enzyme involved in the synthesis of dopamine and serotonin, which are responsible for the communication between neurons in the nervous system.
“Before treatment, our daughter had not met any development milestones. She suffered from oculogyric crises that evolved into hours of pain, and we were told she would be bedridden for life,” said patient organisation Teach RARE founder, Richard Poulin, whose daughter was treated as part of a clinical trial. “We’re thrilled with the EMA approval, and the hope that this milestone brings to other children and families impacted by AADC deficiency.”