Children all across the globe enrolled in a study to evaluate Upstaza, a gene therapy medication, for the treatment of aromatic L-amino acid decarboxylase (AADC) deficiency. As part of their inclusion in the study, the children underwent a procedure to deliver the gene therapy directly to their brains. Adiroop Kumar (4) and his mother traveled to Israel from India so that the boy could undergo surgery. 

As reported by Israel Hayom, Adiroop was diagnosed with AADC deficiency when he was just 6 months old. His parents had never heard of the condition before and didn’t know what it meant for their son’s future. Doctors even told the family that Adiroop would most likely pass away earlier than expected. 

The gene therapy was administered via a 7-hour surgery. So through the trial, the Kumar family found not just treatment, but hope. Hope that their son might live a long and happy life. Hope that there might be an eventual cure. Hope that they can keep their son close for longer. 

Upstaza contains eladocagene exuparvovec, a functional version of AADC, that is delivered using an adeno-associated viral vector. 

An Overview of AADC Deficiency

DDC gene mutations cause aromatic L-amino acid decarboxylase (AADC) deficiency, a rare genetic disorder. These mutations stop the AADC enzyme from working properly. Normally, this enzyme aids in neurotransmitter production. But when the AADC enzyme is deficient, the body doesn’t produce enough dopamine, norepinephrine, epinephrine, or serotonin, causing the disease’s symptoms. In many cases, symptoms appear within the first few months of birth. These may include:

• Hypotonia (low/poor muscle tone) in the trunk and hypertonia (excess muscle tone) in the extremities
• Developmental delays
• Congestion
• Drooping eyelids
• Diarrhea or constipation
• Failure to thrive
• Tremors
• Hypokinesia (loss of muscle movements) 
• Reflux 
• Excessive sweating and salivation
• Temperature instability
• Oculogyric crisis (episodes of uncontrolled head/neck movements, muscle spasms, eyeball/gaze deviation, and irritability) 
• Dystonia
• Seizures

This is not a full list of potential symptoms. In many cases, AADC deficiency is fatal in childhood. However, for people with mild AADC deficiency, lifespan can extend into adulthood. There are no cures for this disorder. Doctors may prescribe dopamine agonists, vitamin B6, pyridoxal phosphate, or monoamine oxidase B inhibitors to help with symptom management.