Novel gene therapy could help children with rare genetic condition walk and talk

A novel gene therapy that targets the brain has been tested in clinical trials to treat Aromatic L-amino acid decarboxylase (AADC) deficiency, a rare hereditary disorder in children.

Called Upstaza, the therapy not only improved the symptoms of all participants in the small-scale trial but also gave some children the ability to walk and talk for the first time.

There is no cure for the condition, yet

AADC deficiency is a genetic condition that affects the nervous system. So far, only around 120 cases have been reported, and about half of these had Asian ancestry.

The condition occurs due to mutations in the DDC gene that encodes a protein needed for synthesizing serotonin, dopamine, and other important neurotransmitters. Therefore, people with AADC deficiency either don't have enough of this protein or a defective version, which prevents them from synthesizing sufficient neurotransmitters.

This leads to complications, such as difficulty coordinating movements, especially of the face, head, and neck. Patients typically have difficulty standing, walking, and talking. They may also have oculogyric crises such as spasms in the eye muscles that fix a person's gaze upward.

There is no cure for the condition yet, but the new gene treatment is a promising development toward easing the symptoms.

Delivering healthy copies of the DDC gene

Upstaza functions by directly delivering healthy copies of the DDC gene to the nerve cells in the brain. In this direction, a small hole is made in the skull, and a modified, harmless virus is then injected into the putamen, the region of the brain involved in learning and motor control that is particularly crucial for speech and movement.

The results, which were presented at the annual symposium of the Society for the Study of Inborn Errors of Metabolism in Freiburg, Germany, have shown that the ability to move and think clearly, as well as experiencing ocular crises, improved in all the 30 children who received the treatment.

"The ones who got it before four years of age, it's quite a dramatic difference," trial lead Wuh-Liang Hwu at the National Taiwan University Hospital told New Scientist. "We say they have been reborn."

According to New Scientist, seven kids reportedly learned to walk, and three learned to talk after getting Upstaza.

In July 2022, Upstaza was authorized by the European Medicines Agency and is now the first approved disease-modifying treatment for AADC deficiency and the first marketed gene therapy directly infused into the brain. Now researchers are looking forward to approval by the US Food and Drug Administration.