Innovative gene therapy “reprograms” cells to reverse neurological deficiencies

A new method of gene therapy is to help children born with a rare genetic disorder called AADC deficiency that causes severe physical and developmental disabilities. The study, led by researchers at Ohio State University’s Wexner Medical Center and Ohio State University College of Medicine, offers new hope to those living with incurable genetic and neurodegenerative diseases.

The results of the research are published online in the journal Communications on Nature.

This study describes the results of targeted delivery of gene therapy to the middle brain to treat a rare deadly neurodevelopmental disorder in children with neurogenetic disease, the aromatic L-amino acid decarboxylase (AADC) deficiency characterized by a deficient synthesis of dopamine and serotonin.

Only about 135 children worldwide are known to lack the enzyme that produces dopamine in the central nervous system, which feeds the brain pathways responsible for motor function and emotions. Without this enzyme, children have no muscle control and are usually unable to speak, feed, or even lift their head. They also suffer from episodes of seizures called eye attacks that can last for hours.

“Surprisingly, these episodes are the first symptom to disappear after gene therapy surgery and never return,” said study co-author Dr. Krystof Bankiewicz, a professor of neurological surgery at Ohio State College of Medicine. who runs the Bankiewicz laboratory. “In the months that follow, many patients experience life-changing improvements. Not only do they begin to laugh and improve their mood, but many are able to start talking and even walk. They are recovering the time that they lost during their abnormal development. “

Gene therapy targeted at seven children aged 4 to 9 years who were infused with the viral vector resulted in a dramatic improvement in symptoms, motor function, and quality of life. Six children were treated at UCSF’s Benioff Children’s Hospital in San Francisco and one at Ohio Wexner State Medical Center. This therapeutic modality promises to transform the treatment of AADC deficiency and other similar brain disorders in the future, Bankiewicz said.

During gene therapy surgery, doctors infuse a benign virus programmed with specific DNA into precisely targeted areas of the brain. The infusion is delivered very slowly, as surgeons control exactly how it spreads to the brain using real-time MRI images.

“Really, what we’re doing is entering a different code into the cell,” Dr. James “Brad” Elder, director of neurosurgical oncology at the Ohio State Wexner Medical Center Neurological Institute. “And we’re seeing everything happen live. So we continually repeat the MRI and we can see the infusion bloom inside the desired nucleus.”

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

The targeted gene therapy, in these patients, resulted in a dramatic improvement in symptoms, motor function, and quality of life. This therapeutic modality promises to transform the treatment of AADC deficiency and other similar brain disorders in the future.