Gene therapy’s promise seen in its success for AADC deficiency

Potential to improve quality of life for people with neurological disorders

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

Share this article:

Share article via email
This illustration of a DNA strand shows its double-helix structure.

The first successes of gene therapy for AADC deficiency highlight the potential that gene therapies have to improve life for people affected by neurological disorders, researchers said in a new review paper.

The paper, “Gene therapy for neurodegenerative disorders in children: dreams and realities,” was published in Archives de Pédiatrie.

Gene therapy is a treatment strategy designed to change the genetic activity of a person’s cells, either by putting a new gene into cells or by altering the DNA inside cells. In principle, gene therapy has the potential to treat many disorders that affect the brain.

However, barriers to developing gene therapies include the fact that researchers must first identify the exact genetic cause of a disorder, then find a way to deliver a therapeutic gene into cells, which can be especially challenging when targeting cells in the brain. Researchers also need to come up with effective ways to measure if the therapy is working, as well as protocols to ensure patient safety in trials.

Two general strategies can be used for gene therapy: ex vivo, where cells from a patient are collected, modified in a lab, then put back into the patient, and in vivo, where cells within a living person are modified, usually using an engineered virus to deliver a therapeutic gene.

Recommended Reading
An illustration of a scientist holding a flashlight to a giant image of a brain while another examines it with a magnifying glass.

Real-time MRI may improve delivery of gene therapy to brain

Upstaza shows gene therapy’s ‘high impact on quality of life’

Upstaza (eladocagene exuparvovec), a gene therapy for AADC deficiency developed by PTC Therapeutics, has been one of the first big success stories for in vivo gene therapy of a neurological disease. The therapy is administered directly into the brain via a surgical procedure, and it works to give brain cells a working version of the DDC gene, mutations in which cause AADC deficiency.

Upstaza has been approved for use in the European Union and in the U.K. based on clinical trial data showing it can improve motor and cognitive function for children with AADC deficiency. PTC is expected to seek approval of Upstaza soon in the U.S.

“All studies reported [improvement] of motor and cognitive performances, in particular in younger participants with milder baseline impairment,” the researchers wrote, noting the improvements seen with the gene therapy had “a high impact on quality of life.”

Currently, only one other in vivo gene therapy for a neurological disease is widely approved — Zolgensma (onasemnogene abeparvovec-xioi) for spinal muscular atrophy. There’s still a long way to go to optimize these therapies and create gene therapies for several other disorders that lack treatments, but the early successes show that gene therapies can be transformative.

“Gene therapy represent a unique therapeutic strategy to reach the brain in order to prevent or halt a neurodegenerative process,” the researchers wrote. “The bottleneck of GT [gene therapy] remains its cost and depends on the capacity of industry to engineering vector. This would justify specific high throughput platforms and innovative financial support and business models for use in clinical practice.”