Rare Daily Staff

A novel method of gene therapy is helping children born with a rare genetic disorder called AADC deficiency that causes severe physical and developmental disabilities.

A study conducted by researchers at The Ohio State University Wexner Medical Center, The Ohio State University College of Medicine, and the University of California, San Francisco offers hope to those living with incurable genetic and neurodegenerative diseases.

People born with AADC deficiency are missing an enzyme that produces dopamine in the central nervous system, which fuels pathways in the brain responsible for motor function and emotions. Without this enzyme, children lack muscle control and are usually unable to speak, feed themselves or even hold up their head. They also suffer from seizure-like episodes called oculogyric crises that can last for hours.

Children in the study experienced improved motor function, better mood, and longer sleep, and were able to interact more fully with their parents and siblings. Oculogyric crisis, a hallmark of the disorder involving an involuntary upward fixed gaze that may last for hours and may be accompanied by seizure-like episodes, ceased in all but one patient.

“Remarkably, these episodes are the first symptom to disappear after gene therapy surgery and they never return,” said study co-author Krystof Bankiewicz, professor of neurological surgery at The Ohio State University Wexner Medical Center and professor of Neurological Surgery
UCSF Weill Institute for Neuroscience. “In the months that follow, many patients experience life-changing improvements. Not only do they begin laughing and have improved mood, but many are able to begin speaking and even walking. They are making up for the time they lost during their abnormal development.”

Bankiewicz developed a viral vector containing the AADC gene. The vector is infused into the brain via a small hole in the skull, using real-time MRI to map the target region and guide the infusion.

Researchers believe this same method of gene therapy can be used to treat other genetic disorders as well as common neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease. Clinical trials are underway to test this procedure in others living with debilitating and incurable neurological conditions.

Significant improvements were reported by parents and caregivers in sleep and mood, as well as in feeding difficulties, such as vomiting, and upper airway obstruction due to profuse mucus secretions and congestion. The procedure was well tolerated without adverse short-term or long-term effects. One child died at seven months after surgery. The patient appeared to be in good health and the researchers said the cause of death is most likely attributable to the underlying primary disease.

The study follows a trial in Parkinson’s disease, which also showed positive results with increased durations of well-controlled symptoms. The Bankiewicz team will start two new gene therapy trials, using the same surgical techniques and viral vector, for early Alzheimer’s disease and for multiple system atrophy, a rare neurodegenerative disorder.

Krystof Bankiewicz, professor of neurological surgery at The Ohio State University Wexner Medical Center

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