Breakthrough

Gene therapy helps children with rare, often fatal disease

By John Pastor

“Subject 1” was bedridden with a rare inherited disease before participating in a gene therapy clinical trial in Taiwan. Pictured here two years later, she smiles and displays greater mobility.

Using gene transfer techniques pioneered by UF faculty, Taiwanese doctors have restored some movement in four children bedridden with a rare, life-threatening neurological disease.

The first-in-humans achievement may also be helpful for more common diseases such as Parkinson’s that involve nerve cell damage caused by lack of a crucial molecule in brain tissue. The results appeared in the journal Science Translational Medicine.

The children in the study inherited a rare disease known as aromatic L-amino acid decarboxylase deficiency, or AADC. Patients with AADC are born without an enzyme that enables the brain to produce the neurotransmitter dopamine. They generally die in early childhood.

In a phase 1 clinical trial led by Wuh-Liang Hwu, M.D., of the National Taiwan University Hospital, surgeons used a delivery vehicle called an adeno-associated virus type 2 vector to transport the AADC gene into localized areas of the brains of three girls and a boy.

Before therapy, the children showed practically no spontaneous movement and their upper eyelids continually drooped. After receiving the corrective gene, the children gradually gained some head movement. Sixteen months later, the children’s weight had increased, one patient was able to stand and the other three were able to sit up without support.

The study shows gene therapy that targets AADC deficiency is well-tolerated and leads to improved motor development and function, according to co-authors Barry Byrne, M.D., Ph.D., director of UF’s Powell Gene Therapy Center, and Richard O. Snyder, Ph.D., director of UF’s Center of Excellence for Regenerative Health Biotechnology.

“This absolutely opens the door to the possibility of even earlier treatment of neurological diseases by direct gene transfer, and has implications for Parkinson’s disease, ALS and even cognitive diseases such as dementia when caused by gene defects,” Byrne said.