Gene therapy for rare brain disease gets nod from EMA

Human brain

A gene therapy targeting a rare brain disorder has received a positive opinion by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA).

PTC Therapeutics’ one-time gene replacement therapy Upstaza was given a positive opinion for the treatment for aromatic L-amino acid decarboxylase (AADC) in patients 18 months or older. It makes it the first marketed gene therapy directly infused into the brain.

The CHMP opinion was based on clinical studies in Taiwan, alongside data from compassionate use treatment of patients in Europe.

Upstaza is a recombinant adeno-associated virus serotype 2 (AAV2)-based gene therapy, containing the human Dopa Decarboxylase (DCC). It’s been developed to correct the underlying genetic defect of patients with AADC by delivering a functioning DDC gene directly into the putamen, increasing the AADC enzyme and restoring dopamine production.

A study of 26 patients who received infusions of the therapy reported rapid improvements in motor and cognitive functions within 12 months, the benefits of which were sustained during a follow up of over five years.1

Patients in the clinical studies developed clinically meaningful motor skills and neuromuscular function from as early as three months following treatment and continued to display improvements up to nine years after treatment. More so, cognitive and communication skills improved in all treated patients.

AADC is a rare disease caused by the decreased activity of certain enzymes which are involved in the building of the dopamine and serotonin neurotransmitters, and which adversely affects the nervous system. The condition leads to decreased muscle tone, delays development and disrupts parts of the nervous system responsible for the heartbeat.2

Official comments

“We are thrilled with the positive opinion from the CHMP, and are eager to bring Upstaza to patients living with AADC deficiency,” said Stuart W. Peltz, Chief Executive Officer, PTC Therapeutics. “Upstaza will be the first marketed gene therapy that is directly administered into the brain, the first gene therapy approved in a major market in several years, the third gene therapy that is on the market now, and only the fourth in vivo gene therapy ever approved. It’s important for the biotech community to have gene therapy products achieving approvals at regulatory bodies, as well as it being an important milestone for PTC that will help us build the gene therapy franchise and grow our revenue base.”

“The difference Upstaza, a one-time gene therapy, can make is life-changing,” said Paul Wuh-Liang Hwu, lead investigator, National Taiwan University Hospital. “AADC deficiency is a devastating neurological disorder with no effective treatment. Before therapy, affected children couldn’t even lift their head, but now many can sit, stand with help, feed themselves and some can walk and talk.”

PTC Therapeutics now expects the European Commission to ratify the marketing authorisation for Upstaza under exceptional circumstances in approximately two months. The decision will be applicable to all 27 European Union member states, as well as Iceland, Norway and Liechtenstein.


1: 1 Tai CH, et al. Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency. Mol Ther. 2022;30(2):509-518.


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