Gene therapy Kebilidi helps boy with severe AADC walk, run: Case report
Dopamine-boosting medication may have helped boost outcomes
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A boy with a severe form of aromatic L-amino acid decarboxylase (AADC) deficiency was able to walk independently — and later run — after receiving the gene therapy Kebilidi (eladocagene exuparvovec), according to a new case report.
The child, now 5, showed rapid and sustained improvements in movement after being treated at about 3 years old. Before that, he had already reached some developmental milestones with dopamine-boosting medications, which researchers say may have helped support his progress while he awaited gene therapy.
“Initiating early dopaminergic treatment is suggested to prevent or potentially slow neurodevelopmental deterioration or stagnation in children with AADC defect, while awaiting gene therapy,” researchers wrote.
The case report, “Potential impact of early pharmacological treatment on gene therapy outcomes in AADC deficiency.” was published in the journal Parkinsonism & Related Disorders.
Boy showed signs of severe disease early in life
AADC deficiency is a rare genetic disorder caused by mutations in the DDC gene that interfere with the function of an enzyme needed to make key neurotransmitters — chemical messengers that nerve cells use to communicate — including dopamine and serotonin.
In this case, the boy showed signs of severe disease early in life. By age 1, he had significant delays in motor development, poor muscle tone, limited spontaneous movement, and frequent oculogyric crises — episodes in which the eyes involuntarily roll upward. He also had extreme irritability, sleep difficulties, excessive drooling, and hip dislocation.
These symptoms prompted further tests, including genetic analysis, which confirmed AADC deficiency.
Before receiving gene therapy, the child was treated with medications commonly used in AADC deficiency, including pramipexole, selegiline, and vitamin B6 (pyridoxine), which aim to boost dopamine signaling or support related pathways.
With these therapies, he achieved head and trunk control, began shuffling, and started producing simple speech sounds. However, key milestones such as standing and walking independently remained out of reach because of severe coordination problems. Oculogyric crises continued to occur frequently and interfere with daily life.
Motor abilities improved substantially after receiving Kebilidi
At 40 months of age, the boy received Kebilidi, a one-time gene therapy designed to deliver a functional copy of the DDC gene directly to the brain through a minimally invasive neurosurgical procedure. This allows brain cells to produce the missing enzyme and increase dopamine and serotonin production.
Within days, his oculogyric crises disappeared, and his motor abilities improved substantially over the following months. He was able to stand with support within three months, walk independently within a year, and run about six months later. Two years after treatment, he could perform more complex movements such as jumping steps.
Standardized assessments confirmed broad improvements in both gross and fine motor skills, particularly in areas related to movement and coordination.
The boy also showed improvements in cognitive skills, including the ability to concentrate on a given task, process information, and engage in exploratory play. His ability to understand familiar words and simple commands also improved, and his vocabulary expanded.
Still, speech remained one of the most affected areas. By age 5, the boy was using mostly single words or short phrases, and his speech continued to have noticeable errors.
Despite a very severe presentation, our patient showed significant improvement with dopaminergic treatment, shifting to a milder [disease presentation] than that of other treated patients. This suggests that early dopaminergic treatment could prevent some of the most severe and irreversible neurodevelopmental consequences of early chronic dopamine depletion.
The researchers also reported improvements in daily living and social skills, as well as in executive function — a set of mental skills used to manage everyday tasks such as planning, problem-solving, and adapting to new situations. However, the boy continued to have challenges with attention, impulse control, and emotional regulation.
Importantly, as his condition improved, doctors were able to stop or reduce some of his medications without worsening symptoms. Follow-up analysis of spinal fluid showed a modest increase in dopamine metabolites, consistent with increased dopamine production after treatment.
Because AADC deficiency can vary widely from child to child — even among those with the same genetic mutation — a single case cannot predict how others will respond. Still, the findings add to growing real-world evidence that gene therapy can lead to meaningful improvements, even in children with severe disease.
The report also suggests that starting dopamine-boosting medications early may help support development and possibly improve outcomes while waiting for access to gene therapy.
“Despite a very severe presentation, our patient showed significant improvement with dopaminergic treatment, shifting to a milder [disease presentation] than that of other treated patients. This suggests that early dopaminergic treatment could prevent some of the most severe and irreversible neurodevelopmental consequences of early chronic dopamine depletion,” the team concluded
