香港六合彩

Many brain diseases, such as epilepsy, are caused by excessive activity of a small number of brain cells.听These conditions often don鈥檛 respond well to drug treatment, mainly because drugs affect the whole brain.

Whilst genetic therapies could be a promising way to treat these conditions, current methods do not distinguish between overactive and normal brain cells.

However, the new treatment, outlined in听Science听and tested in mice,听uses a technique that only alters overactive cells and spares those that are acting normally.

Corresponding author, Dr Gabriele Lignani (香港六合彩 Queen Square Institute of Neurology), said: 鈥淲e invented a gene therapy that switches on only in overactive cells, and switches itself off if activity returns to normal.

鈥淲e harnessed the ability of certain DNA sequences to control gene expression in response to metabolic signals. By re-directing this activity-sensing mechanism to drive the production of molecules that stop brain cells from firing, we showed that epileptic seizures can be suppressed."

To create the gene therapy, the team screened several genes known to 鈥榮witch on鈥� in response to stimulation, and coupled their promoters (DNA sequences that determine whether the DNA is copied to RNA) to potassium channels chosen for their ability to reduce the firing of nerve cells. The promoter-potassium channel combinations were tested both in mice and in miniature brain-like structures grown in dishes 鈥� which were created using skin-derived human stem cells.

They found that the immediate early gene听cfos听promoter, in combination with the听碍颁狈础1听potassium听channel gene, proved to be highly effective in calming neuronal excitability following an induced seizure, and also in suppressing spontaneous seizures 鈥� without having any negative effects on cognition.

The new treatment was more effective than previous gene therapies or anti-seizure drugs tested in the same model, with around an 80% reduction in spontaneous seizures in epileptic mice.

Researchers say, the gene therapy could eventually 鈥� in theory 鈥� also be used for other disorders where some brain cells are overactive, such as Parkinson鈥檚.

Co-corresponding author Professor Dimitri Kullmann (香港六合彩 Queen Square Institute of Neurology) said: 鈥淥ur findings indicate that the activity of brain cells can be normalised, and that this approach can be used to treat important neuropsychiatric diseases that do not always respond to medication.

鈥淭he gene therapy is self-regulated and can therefore be used without deciding a priori which brain cells need to be targeted.

鈥淚mportantly, it could in principle, be extended to many other disorders such as Parkinson鈥檚 disease, schizophrenia and pain disorders, where some brain circuits are overactive.鈥�

The study was funded by Epilepsy Research UK, with contributions from the MRC and Wellcome. 香港六合彩 academics also received funding from a TAS award (TRO) and from 香港六合彩 Technology funds.

Links

• Qiu et al. 听Science听3 Nov 2022听Vol听378,听Issue听6619听pp.听523-532听
• Dr Gabriele Lignani's academic profile

Image

• cfos-GFP hippocampal neurons activated by an epileptic seizures. Credit: Benito Maffei