Brain repair
The adenovirus vector delivered the missing enzyme to the children's brains and saved them from seizures
Anastasia Kuznetsova, N+1
American scientists, using an adenovirus vector, delivered the enzyme decarboxylase of aromatic amino acids to the children's brains, which did not work for them. This helped the brain cells to start synthesizing dopamine from levodopa again, so the children stopped having motor crises after a few months, and half of them were able to sit on their own. Doctors told about the study in Nature Communications.
Dynamics of dyskinesia level after gene transfer
Deficiency of aromatic amino acid decarboxylase is a rare genetic disease, since the 90s only about 100 cases of this disease have been described. Due to the disruption of this enzyme, there is a deficiency of serotonin, dopamine, norepinephrine and adrenaline. The first symptoms in children appear at the age of several months. They lag behind in development, they have problems with initiation and control of movements, their muscles lose tone. One of the most typical and severe symptoms of the disease is oculogyric crises, which are accompanied by a friendly deviation of the eyes to one side and can last for several hours. This disease is considered incurable, and it is only possible to alleviate its symptoms by prescribing, for example, dopamine agonists or monoamine oxidase inhibitors that destroy serotonin, adrenaline, dopamine and norepinephrine.
Scientists have hypothesized that if decarboxylase of aromatic amino acids is delivered to the brain of children using an adenovirus vector, it will improve their condition. Attempts to use this method of treatment have been made in Taiwan and Japan: the viral vector was injected into the brain shell of children (one of the basal nuclei that control movement). Therapy improved the condition of the children, but oculogyric crises continued to appear. Only 2 out of 12 children could sit without support after treatment.
American doctors led by Kristof Bankiewicz (Krystof S. Bankiewicz) from The University of California decided to try to change the region of enzyme delivery. Their target was the black substance and the ventral area of the tire. Dopamine pathways start from these regions, so their neurons produce levodopa, which aromatic amino acid decarboxylase converts into dopamine. The study recruited 7 children with aromatic amino acid decarboxylase deficiency aged 4-9 years. Under the control of magnetic resonance imaging, a needle was inserted into the black substance and ventral region of the tire and an adenoviral vector carrying the aromatic amino acid decarboxylase gene was delivered to the children.
After 3 months, the concentration of dopamine metabolites was measured in children using positron emission tomography. In all patients, it increased significantly compared to the levels before surgery (p=0.0078). Oculogyric crises stopped in 6 out of 7 children, on average it took 9-33 days after surgery. Also, half of the participants were able to sit without support after a few months, and 2 children began to walk with crutches. No side effects of treatment were registered in any child.
Scientists hope that in the future this method of treatment can be used to treat other genetic diseases. The researchers were surprised how quickly the brain recovered the lost motor functions, but concluded that in children, genetic therapy should be started as early as possible.
Aromatic amino acid decarboxylase was also delivered to the brains of patients with Parkinson's disease, as their production of this enzyme decreases over time. After 12 months, the patients' motor functions and quality of life improved.
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