One-time gene therapy sees promising results in children with AADC deficiency
pharmafile | August 25, 2021 | News story | Research and Development |
A pioneering approach to gene therapy delivery has been published in the European Molecular Biology Organization Journal on Wednesday, wherein a specific part of the brain is targeted to successfully treat a previously intractable disorder in children.
AADC deficiency (AADC-d) is a debilitating neurological disorder that involves motor dysfunction caused by dopamine deficiencies, and currently has no approved disease-modifying therapies.
Researchers have successfully treated children with AADC-d in Phase III clinical trials by targeting the part of the brain called the putamen with their gene therapy, PTC-AADC.
Stuart Peltz, Chief Executive Officer of PTC Therapeutics, said: “AADC deficiency is a terrible, life-shortening condition that requires around-the-clock care. The data reported in this article show that the surgical approach of delivering our novel PTC-AADC gene therapy directly to the putamen robustly produces dopamine in the brain that results in sustained and substantial functional improvements in children with AADC deficiency.”
The paper, authored by researchers in the US, Taiwan, France, Germany, and Japan, describes three clinical trials in which AAV2-hAADC was infused into the putamen of children with AADC-d via brain surgery.
Prior to treatment, most of the children with AADC-d had never developed muscle control, could not lift their heads, move on their own or talk, and nearly all were bed ridden. Every child in the trials showed significant improvements following treatment with PTC’s novel gene therapy, PTC-AADC.
Dopamine (DA) is a neurotransmitter that is critical for motor and mental development and the studies have demonstrated that the restoration of DA synthesis in the putamen via gene therapy using low doses of AAV2-hAADC, leads to sustained improvements in motor and nonmotor symptoms of AADC deficiency, and beneficial for the patients.
The gene therapy, PTC-AADC was delivered to the putamen because it is more easily accessible via surgery than other sites, and therefore, may result in fewer surgical complications. In neurological disorders such as AADC-d, the putamen is directly impacted by the loss of DA synthesis in the striatum.
Paul Wuh-Liang Hwu, from the National Taiwan University Hospital, said: “The remarkable results published have been life-changing for the children we have treated.
Before this treatment, the children with AADC deficiency couldn’t lift their heads, but now some can sit and stand with help, and have even begun learning to talk.”
PTC-AADC is currently under review by the European Medicines Agency’s Committee for Medicinal Products for Human Use with an opinion expected in the fourth quarter of 2021.
Kat Jenkins
