Pediatric AADC Deficiency Improves With New Gene Therapy

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This new analysis of 5-year data on a novel gene therapy from PTC Therapeutics shows both cognitive and motor function improvement in children with aromatic L-amino acid decarboxylase (AADC) deficiency, a rare central nervous system disorder.

Pediatric aromatic L-amino acid decarboxylase (AADC) deficiency, a rare chronic disorder that is often marked by death in childhood, severe disability, and necessary breathing support, may have a novel treatment option in a new gene therapy from PTC Therapeutics that can be administered just once.

The central nervous system disorder is characterized by the defective DDC gene that leads to dysregulation of body control, movement, and cognitive skills—because of a lack of the AADC enzyme leading to impaired dopamine production—leaving children unable to hold their head up, sit and stand unassisted, or speak. They also frequently have behavioral, sleeping, cardiovascular, gastrointestinal, endocrine, and respiratory difficulties; developmental delays; and decreased muscle tone.

“The transformations we are seeing in the children are remarkable,” said Stuart W. Peltz, PhD, CEO, PTC Therapeutics, in a statement. “Treatment with PTC-AADC is restoring dopamine production, which leads to the children now being able to sit, roll over, stand and walk. They are also able to communicate and gain both weight and strength.”

The gene therapy is directly administered to the putamen site of the brain, which utilizes dopamine.

PTC’s analysis of 5-year data from 3 clinical trials shows the following results:

  • Improvements seen for motor function persisted through 10 years and could be seen as soon as 3 months following administration.
  • Cognitive and language improvements from baseline, gauged via Bayley-III scores, demonstrated children could understand their caregivers and express themselves.
  • Respiratory infections declined consistently: from 2.4 to 0.6 to 0.3 annual episodes at 1, 2, and 5 years, respectively, following administration.
  • Most children who received PTC-AADC achieved age-appropriate weight gains in the year after treatment compared with being below the third percentile in weight at baseline.

As an investigational new drug in the United States, a biologics license application to the FDA is expected from PTC Therapeutics by year-end. Meanwhile, in Europe, the investigative agent is being reviewed by the European Medicines Agency's Committee for Medicinal Products for Human Use, and that opinion also is expected by year-end.

“The impact that this one-time gene therapy has had on children with AADC deficiency in these trials is truly life-changing,” said investigator Paul Wuh-Liang Hwu, MD, PhD, National Taiwan University Hospital. “We are encouraged by the strong safety profile and long-lasting effect seen with PTC-AADC, and how it has improved the lives of patients and their caregivers.”


Results show long-lasting and holistic improvements in children with AADC deficiency treated with PTC-AADC gene therapy. News release. PTC Therapeutics. September 20, 2021. Accessed October 1, 2021.