New gene therapy targets overactive brain cells to treat neurological disorders
In a recent study researchers developed a new treatment for neurological and psychiatric diseases that reduces the excitability of overactive brain cells.
The study, published in the journal, Science, was conducted by researchers from University College London (UCL). While there are several promising genetic therapies for neurological conditions, few distinguish between overactive and normal brain cells. For their investigation, researchers sought to use gene therapy to alter overactive cells and protect the ones acting normally.
Scientists developed the therapy first by screening several genes know to “switch on” in response to stimulation. Next, they coupled the gene’s DNA sequences known as promoters, that are responsible for copying DNA into RNA, to potassium channels that could reduce the firing of nerve cells. These promoter-potassium channel combinations were later tested in mice as well as miniature brain-like structures with skin-derived human stem cells.
The immediate early gene cfos promoter in combination with the KCNA1 potassium channel gene was highly effective in calming neuronal excitability after an induced seizure, according to the study. In addition, the promoter-potassium combination was able to suppress spontaneous seizures without having negative effects on cognition. Researchers determined that the treatment resulted in a 90 percent reduction in spontaneous seizures in epileptic mice, proving to be more effective than previous gene therapies.
According to investigators, these results suggested that this therapy can normalize activity in brain cells and can be used to treat neuropsychiatric diseases that don’t always respond to medication.
“The gene therapy is self-regulated and can therefore be used without deciding a priori which brain cells need to be targeted,” said Dimitri Kullmann, MD, of the UCL Queen Square Institute of Neurology. “Importantly, it could in principle, be extended to many other disorders such as Parkinson’s disease, schizophrenia and pain disorders, where some brain circuits are overactive.”