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AADCd Gene Therapy Trials: USA

Target Area Substantia Nigra Pars Compacta & Ventral Tegmental

Click on the flag for more information on our sister page: Gene Therapy Treatment: Poland... 

AADC deficiency is caused by mutations in a single gene called DDC. Because of these mutations patients are unable to produce two chemicals called dopamine and serotonin. These chemicals act as neurotransmitters to carry signals between nerve cells in the brain. Current treatments for AADC deficiency try to increase or replace these chemicals but do not work well for most patients and often have serious side-effects. New treatment options are desperately needed to help the patients affected by this disorder. In response to this a clinical trial of gene therapy for AADC deficiency is taking place at the University of California San Francisco (UCSF), USA. The aim is to transfer a functional copy of the AADC gene into the specific part of the brain where AADC is normally found. This should act like a replacement for the patient’s dysfunctional gene and allow the patient to produce neurotransmitters.

The Gene Vector

The trial will make use of technology that was originally designed to treat Parkinson’s disease. A special type of viral vector, has been developed that contains the AADC gene. The vector acts as a delivery system to transfer the gene into the patient’s cells. The full name of the vector is

adeno-associated virus serotype 2 (AAV2). The AAV2 vector has already been used in gene therapy trials for a number of different diseases. The AAV2 vector containing the human AADC gene is called AAV2-hAADC. The vector is manufactured in a specialist facility at the Children’s Hospital of Philadelphia. The vector is produced inside cells, purified and filtered within the facility. This facility operates to Current Good Manufacturing Practice (cGMP) standards and is regulated by the U.S. Food and Drug Administration (FDA).

The Surgery

In order for the AAV2-hAADC vector to be delivered to the correct brain cells it needs to be directly injected into a specific region of the brain. Professor Krystof Bankiewicz and his team have developed pioneering surgical techniques to ensure accurate delivery of a vector to the selected brain region. The system uses a specially designed cannula that is inserted into the brain to allow direct infusion of a liquid containing the AAV2-hAADC vector. The patient’s head is placed in a specialised stereotactic frame and cannula guide devices are attached. Real-time MRI imaging of the patient’s brain is used to map the target region, plan cannula insertion and positioning, and calculate how much vector to infuse. Brain imaging is performed throughout the surgery to guide the cannula to the target site and a special gadolinium tracer will enable the surgeons to visualise the spread of the vector. Following delivery the cannula is removed and the incision is closed by the surgeons. Following surgery the patients are cared for and closely monitored.

The Targeted Brain Region

The nerve cells that use dopamine in the brain are organised into a series of pathways. These pathways connect one part of the brain to another with the nerve cells acting like wires between them. There are three major Dopaminergic pathways: the mesocortical pathway, the mesolimbic pathway and the nigrostriatal pathway. The mesocortical and mesolimbic pathways both start in a brain area called the ventral tegmental area (VTA) and the nigrostriatal pathway begins in an area called the substantia nigra pars compacta (SNpc). Both the VTA and SNpc are found in an area of the brain called the mid-brain. For this reason Prof. Bankiewicz plans to target the mid-brain region in the gene therapy clinical trial for AADC deficiency. The hope is that by targeting the mid-brain all three of these pathways will receive the functional AADC gene. Additionally, previous work from the Bankiewicz lab has demonstrated that the AAV vector is able to be transported from the start of a pathway to the end (anterograde transport) but not from the end to the start (retrograde transport). By targeting the start of the dopamine pathways it is suggest that the AADC vector will be transported to the ends of the pathways and hopefully increase the effectiveness of treatment. One of the major differences between Prof. Bankiewicz’s trial and the ongoing gene therapy trial in Taiwan is the brain area that is targeted. In the Taiwanese trial they have been targeting a different area of the brain called the putamen, which is the end point of the nigrostriatal dopamine pathway.

The initial clinical trial will treat 6 children with AADC deficiency and a second trial site is imminent.

The AADC Research Trust is strongly supportive of this gene therapy clinical trial. The Trust awarded 45,000 USD to Prof. Krystof Bankiewicz to aid preparation of an application to the FDA for Investigational New Drug (IND) status.

Phase 1 of AAVZ-hAADC Clinical Trials is almost complete and we were lucky enough to hear about these updates from Professor Krsytof Bankiewicz and Doctor Toni Pearson at our 4th World Conference in November 2018, as per video below...

Professor Krystof Bankiewicz and Dr Toni Pearson:

Update on AAV2-hAADC Gene Therapy Trials in Primary AADCd Paediatric Patients (Target Area VTA and SNpc)

KP1X5 News Report on AADCd Gene Therapy under Krystof Bankiewicz, USA

Finally, we can report on the six AADCd children that have received Gene Therapy on the USA trials, under Professor Krystof Bankiewicz at the UCSF Benioff Children’s Hospital, San Francisco.

Click on the image below for the News Broadcast by KPIX5, an American news channel, reporting on the treatment:

"Experimental Therapy Gives Children With Genetic Disorders A New Chance At Life" by Juliette Goodrich and Molly McCrea for KPIX5 19/03/19

Screenshot 2019-03-21 10.53.54.png

Quote from the report :

“These parents are all internet savvy, and found out about the trial online. They gleaned valuable information from the AADC Research Trust which is based in the United Kingdom. The trust is a charity organization that is dedicated to helping these children and their families. The trust has identified 130 children in 26 different countries who have been correctly diagnosed with AADC deficiency.”

The Columbus Children's Foundation

The Columbus Children's Foundation :

Our mission is to accelerate access to the most advanced and effective therapies to treat children diagnosed with ultra-rare monogenic neurodegenerative diseases. At the Columbus Children’s Foundation, we are deeply driven by the urgency to improve the quality of life for children with life-threatening illness.

Gene Therapy is changing the way we see genetic disease. By targeting faulty or missing genes, this innovation is creating a new world of opportunity. 

Title: "Amazing advances in the treatment of childhood Parkinson's"

Published: 17/02/2019

Country: USA / Poland

AAV2-hAADC Gene Therapy Trial Recruitment:

This trial is ACTIVE and RECRUITING.

If you are interested in registering for this trial please click on the link to find out more information. The email contact details are at the bottom of the link page..

A Single-Stage, Adaptive, Open-label, Dose Escalation Safety and Efficacy Study of AADC Deficiency in Pediatric Patients (AADC)


Krystof Bankiewicz



National Institutes of Health (NIH)


Information provided by (Responsible Party):

Krystof Bankiewicz, University of California, San Francisco

AADCd Gene Therapy Journeys...
 Click on the links for more information on Logan's, Audrey's and Alex's Gene Therapy Journeys...

Alex pic.jpg

"It is life changing experience"


"The quality of life improvement for the child is immeasurable and it offers hopes to the child as they continue to improve and develop after the GT"

Ashlee (Alex's mum)

Latest News...

2020 brought many challenges with the emergence of COVID-19. Many aspects of our lives have been put on hold.


Essential surgeries, including AAV2-hAADC Gene Therapy Treatment, had to be postponed due to the extremely difficult circumstances posed by the threat of COVID.


However, Professor Bankiewicz and his incredible team have gone to extraordinary lengths to meet that challenge...


Jamell, aged 6 years old, from the USA, received Gene Therapy in October ...

Jamell post GT.jpg
AAV2-hAADC Gene Therapy Publications...

A safety study was carried out in preparation for AADC gene therapy which is detailed in this publication:

San Sebastian, W., Kells, A. P., Bringas, J., Samaranch, L., Hadaczek, P., Ciesielska, A. and

Bankiewicz, K. S. (2014). Safety and tolerability of MRI-guided infusion of AAV2-hAADC into the mid-brain of non-human primate. Molecular Therapy. Methods & Clinical Development, 3, 14049.

Realtime MRI - Target Structure, Therapeutic Infusion.

The Bankiewicz Laboratory University of California, San Francisco

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