Texas Children's Hospital
October 01, 2025
Texas Children’s is pleased to announce that a three-year-old girl has been successfully treated with the first-ever FDA-approved gene therapy treatment for AADC deficiency.
Aromatic l-amino acid decarboxylase (AADC) deficiency is an extremely rare, inherited neurological disorder that prevents the brain from producing dopamine and serotonin — essential chemicals for controlling movement, mood and basic nervous system functions. The literature reports approximately 350 people with this condition worldwide. Historically, there was no cure or approved treatment for AADC, and the shortened life expectancy was estimated between five and seven years of age.
“Texas Children’s was the largest contributor to the clinical trial in the U.S. that led to this drug’s approval,” said Dr. Daniel J. Curry, who performed the six-hour surgery. Dr. Curry is Director of Functional Neurosurgery and Epilepsy Surgery at Texas Children’s Hospital and Professor of Neurological Surgery at Baylor College of Medicine. “Before now, AADC deficiency was a hopeless diagnosis. With this treatment, we’ve entered a whole new era where we can deliver solutions to formerly untreatable genetic problems. This is the first step in hopefully many future strides toward the molecular correction of inborn deficits for which there used to be no cure.”
Kebilidi (eladocagene exuparvovec-tneq) was approved on November 13, 2024, after a clinical trial involving Texas Children’s Hospital and two other testing sites. It is a modified adeno-associated virus serotype 2 (AAV2) vector-based gene therapy administered by a neurosurgeon directly into the brain’s putamen area, which is involved in learning and motor control. The procedure is a minimally invasive stereotactic neurosurgery that includes four infusions during one surgical session.
The Texas Children’s patient who received the treatment, a 3-year-old girl, first showed signs of developmental delay when she was 7 months old. She had poor muscle control and difficulty holding up her head — one of the common symptoms of AADC deficiency, along with muscle weakness, movement disorders and seizures. Genetic testing confirmed her diagnosis when she was 18 months old, and her local care team has managed her condition with medication and physical therapy until this breakthrough treatment at Texas Children’s became available.
“The treatment was successfully administered with no complications,” said Dr. Curry. “After a two-week stay in the hospital for follow-up care and monitoring, she and her family are now back home and feeling very optimistic. The therapy is expected to take 2-6 months to show measurable impact, but she is already showing signs of increased energy and happiness.”
Dr. Curry helped develop the Texas Children’s Intracerebral Gene Therapy Program with investigations into intraputamenal gene therapy for AADC deficiency, as well as investigations into gene therapy for Rett syndrome and NGLY-1 deficiency. Dr. Curry is also Director of the Neuroinfusion Service at Texas Children’s, conducting intracerebral enzyme replacement therapy in Batten’s disease and other neurodegenerative diseases.
“With these exciting advancements in gene delivery and surgical precision, we can not only treat the root cause of diseases in the brain, but hopefully reverse them,” said Dr. Curry. “This will make a life-changing difference for so many patients.”
https://www.texaschildrens.org/content/news-release/texas-childrens-provides-new-breakthrough-treatment-for-patient-with-rare
Tai CH, Lee NC, Chien YH, Byrne BJ, Muramatsu SI, Tseng SH, Hwu WL. Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency. Mol Ther. 2022 Feb 2;30(2):509-518. doi: 10.1016/j.ymthe.2021.11.005. Epub 2021 Nov 8. PMID: 34763085; PMCID: PMC8822132.
Abstract
Aromatic L-amino acid decarboxylase deficiency results in decreased neurotransmitter levels and severe motor dysfunction. Twenty-six patients without head control received bilateral intraputaminal infusions of a recombinant adeno-associated virus type 2 vector containing the human aromatic L-amino acid decarboxylase gene (eladocagene exuparvovec) and have completed 1-year evaluations. Rapid improvements in motor and cognitive function occurred within 12 months after gene therapy and were sustained during follow-up for >5 years. An increase in dopamine production was demonstrated by positron emission tomography and neurotransmitter analysis. Patient symptoms (mood, sweating, temperature, and oculogyric crises), patient growth, and patient caretaker quality of life improved. Although improvements were observed in all treated participants, younger age was associated with greater improvement. There were no treatment-associated brain injuries, and most adverse events were related to underlying disease. Post-surgery complications such as cerebrospinal fluid leakage were managed with standard of care. Most patients experienced mild to moderate dyskinesia that resolved in a few months. These observations suggest that eladocagene exuparvovec treatment for aromatic L-amino acid decarboxylase deficiency provides durable and meaningful benefits with a favorable safety profile.
Keam SJ. Eladocagene Exuparvovec: First Approval. Drugs. 2022 Sep;82(13):1427-1432. doi: 10.1007/s40265-022-01775-3. PMID: 36103022.
Abstract
Eladocagene exuparvovec (Upstaza™) is a gene therapy developed by PTC Therapeutics for the treatment of human aromatic L-amino acid decarboxylase (AADC) deficiency. Eladocagene exuparvovec comprises an adeno-associated virus vector that delivers the dopa decarboxylase (DDC) gene, the gene for human AADC. Eladocagene exuparvovec was approved in July 2022 in the EU for the treatment of patients aged 18 months and older with a clinical, molecular, and genetically confirmed diagnosis of AADC deficiency with a severe phenotype (i.e. patients who cannot sit, stand or walk). This article summarizes the milestones in the development of eladocagene exuparvovec leading to this first approval for the treatment of patients aged 18 months and older with AADC deficiency.
See: https://childnervoussystem.blogspot.com/2024/11/eladocagene-exuparvovec-for-aromatic-l.html
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