Will Gene Therapy Save These Children with Rare AADC Deficiency?


The young patients began laughing, and some even began to speak and walk.

Imagine the excitement among the hospital staff when they realized that a new medication brought about these major improvements. The UCSF News is on board with a progress report while the July 2021 issue of Nature Communications published details of interim trial results.

Only 135 children in the world are found to be deficient in the AADC enzyme. Children of Asian descent are most likely to develop the disease.

Seven young patients have a genetic disease that causes motor developmental delay and disability. The children, ages ranging from four to nine, are deficient in the AADC enzyme. This enzyme is critical to converting levodopa into the neurotransmitter dopamine that affects learning, movement, and mood.

Neurotransmitters carry messages that affect the limbs, heart, and other organs. They are a repository for information from internal parts of the body.

A deficiency in AADC creates many challenges for patients. One of the most important challenges is their inability to feed themselves. Most patients are unable to keep their heads in an upright position.

 The Gene Therapy Trial

Six children are participants in the gene therapy trial conducted at San Francisco’s Benioff Children’s Hospitals. A seventh child receives treatment at Ohio’s Wexner Medical facility.


The study participants showed an improvement in their mood, sleep, and motor function. The families were buoyed by the children’s improved interaction with their siblings and parents.

A common symptom called Oculogyric crisis often accompanies the disease. It usually involves a type of seizure and a fixed gaze that may last for hours. The researchers found that after surgery, the Oculogyric crisis completely disappeared in six of the seven patients.

Krystof Bankiewicz, senior author of the study and a member of UCSF’s Neurological Surgery Unit, duplicated certain techniques that are used in the treatment of Parkinson’s disease.

Although there are similarities between the two diseases, in Parkinson’s disease the dopamine-producing neurons decline, while in AADC deficiency, the AADC gene is missing. These children do not have an AADC gene that is functional.

To clarify, both diseases involve deficiencies of AADC. Dr. Bankiewicz created a viral vector, which is a harmless version of a virus, that contains the AADC gene. A small opening is created in the skull. The surgeon maps the target area and plans for the infusion of a corrected gene in the AADC patient’s midbrain.

Encouraging Results of AADC Treatment

After gene delivery, researchers found an increase in brain activity. Screening of cerebrospinal fluid found higher concentrations of neurotransmitter metabolites.

When the study began, only two children were able to move their heads. Only one child was able to reach and grasp. None of the children were able to sit without support. With the exception of one child, the children were described as being irritable. Their motor skills were rated as severely impaired.

After Surgery

Symptoms diminished after surgery. Oculogyric crisis symptoms not only disappeared, but never returned. Families described the after-surgery improvements as life-changing. Motor function improved; trunk, head control and limb movements improved.

By the 12th month, four children could sit without support and three children were able to walk with trunk support.

One patient began to take unsupported steps 2 ½ years after surgery. Another child developed a small vocabulary and was able to speak one year after surgery. A second child used a device to communicate in the second year after surgery. The families were overjoyed, as they reported significant improvements.

Difficult feeding problems were addressed. Prior to the surgery, the children were plagued with vomiting and obstruction in the upper airway as a result of congestion and mucus secretions.

There was one fatality. The death occurred seven months after the child’s surgery. The researchers speculated that the underlying disease caused the child’s death.

Alzheimer’s disease and multiple system atrophy are the next disorders to be tested. The same surgical procedures will be used. The trials will be conducted at Ohio University next month.


Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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