Most people have never heard of AADC deficiency. For the few families affected, that is a blessing.
AADC deficiency is a rare genetic disorder that affects about 135 children worldwide. The disease severely disrupts brain function and development.
Children with AADC deficiency often cannot speak, feed themselves, or hold up their heads. Many experience severe mood swings and chronic insomnia.
There is currently no cure.
Researchers at the University of California, San Francisco (UCSF) are working to change that.
A Rare Disease With Devastating Effects
Dr. Krystof Bankiewicz and his team have adapted a gene therapy approach originally developed for Parkinson’s disease.
CIRM currently supports Dr. Bankiewicz’s Parkinson’s clinical trial.
Children with AADC deficiency lack a critical enzyme needed to produce dopamine and serotonin. These chemical messengers help brain cells communicate.
Without them, the brain cannot function normally.
To address this problem, researchers used gene therapy to deliver a healthy copy of the AADC gene directly to the brain.
Surgeons created a small opening in the skull and targeted two key regions of the brainstem: the substantia nigra and the ventral tegmental area.
These regions play important roles in movement, behavior, and neurological function.
Gene Therapy Delivers Remarkable Improvements
When the clinical trial began, all seven children faced profound disabilities.
None could sit independently.
Only two could control their head movements.
Just one child could grasp an object.
Six experienced severe irritability or mood problems, and six struggled with insomnia.
The results surprised even the researchers.
“Remarkably, these episodes were the first to disappear, and they never returned,” said Dr. Bankiewicz. “In the months that followed, many patients experienced life-changing improvements.”
Some children began laughing more often and showed improved mood. Others developed new communication skills. Several gained mobility that had previously seemed impossible.
After one year:
- All seven children improved their head and body control.
- Four children could sit independently.
- Three children could grasp and hold objects.
- Two children could walk with assistance.
New Hope for Children and Families
The improvements continued over time.
Two and a half years after treatment:
- One child could walk without support.
- One child developed a vocabulary of about 50 words.
- One child communicated using an assistive device.
Parents also reported major improvements in sleep and behavior.
These gains may seem modest to healthy individuals. For families affected by AADC deficiency, they are transformative.
The therapy does not cure the disease. Yet it has given children abilities they never had before and families reasons to hope for the future.
Videos released by UCSF show dramatic differences before and after treatment. Children who once struggled to control basic movements can now sit, communicate, and in some cases walk.
For a condition with no effective treatments, that progress represents something extraordinary.
It represents the possibility that gene therapy can change the course of a devastating disease and improve the lives of children who previously had few options.UCSF posted videos of the children before and after surgery, and you can see the big difference. It’s not a cure, but for families that had nothing in the past, it is a true gift.
The study is published in the journal Nature Communications.
Do you take out extra genes? I have C9orf72 ALS.
Sorry Melissa, we don’t do any research, we just fund it. And I don’t know of any researcher who is currently taking out genes.
Kevin what is the latest on macular?? Thanks, Bill
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Hi Bill, here’s a relatively recent article with updated news and information:
https://www.brightfocus.org/macular/article/stem-cell-therapy-and-dry-age-related-macular-degeneration-risks-and-considerations
I hope this helps.
Kevin
AADC deficiency is one of genetic disorders caused by changes or mutation in DDC gene. The gene is critical to express AADC enzyme and provide instructions to the body for functioning. DOPA decarboxylase (DDC) is responsible for the synthesis of the key neurotransmitters called dopamine and serotonin.
Results of gene therapy in children with deficiency of AADC enzyme showed that an improvement of at least one action among the children after treatment, such as better control of head and body movements, sitting up, reading and so on. The disporpotional of neurons transfected with functional gene of AADC in two regions brainstem caused both substantia nigra and ventral degmental developed suboptimum of health in children. The inefficiency of gene therapy to transduce 100% of neurons caused partially recovery of children from their illnesses. In addition, children with different age groups have different requirement of dosages for transfected neurons with AADC to gain optimum health. However, the promoter of most viral carriers have lost ability to control the expression levels of AADC enzyme for requirement of each individual.
This is in contrast to the patients with Parkinson’s disease (PD), the damage or death of nerve cells or neurons in substantia nigra of brain trigger low dopamine secretion and cause them experience the movement related problems. It is uncertain the key factors to cause PD but genetics and environmental factors are likelihood to induce PD in people. Most people develop disorder are over age of 50. Thus, age is considered the greatest risk factor to develop PD. In reviewing the life cycle of humans which can be divided into 5 stages of development, these include infant, puberty, adolescent, menopause and elderly. The endocrine system release variety of growth factors and hormones to regulate entire of life for humans to grow. Evidence proved that all cells require growth factors and hormones for proliferation, differentiation, behavior and survival. Therefore, the regulation of endocrine system becoming subsides during people approaching old age. The lack of growth factors cause the integrity of cell loss and genetic of cell easily to mutate, neurons become highly susceptibility to pollutants and loss affinity of growth factor receptors on neurons of brain might be the risk factors to induce PD in man. iPSCs technology to develop stem cells therapy for old generation may not be rewarded unless prior treatment of cells to turn around the unhealthy into healthy cells.
Fantastic progress. We need to push this technology and innovate as much as we can, to improve the lives of children and adults alike.
Hi there,
How do other families have their child undergo this therapy? When will it be available for other children to benefit from this? My daughter is turning 17 years old and has GRIN2B, with same Simptoms as these children in your study. It would be amazing if this could work for her.
Hi Josie, I’m afraid I don’t know when this will be available for other children. The research is moving ahead as quickly and safely as possible but predicting when or even if it would be approved by the FDA for wider use is impossible.
I see. Well, thanks so much for your response. It’s just so heartbreaking as a parent to try everything and yet your child is still unable to speak or walk unaided or be able to do daily things on her own like feed herself or be out of diapers. Just heartbreaking as a parent to know she is in there but we haven’t found a cure yet. I can’t wait for that day. Hopefully it will happen.