A new compound targeting the protein Pumilio as an antiepileptic drug
Regular functioning of the brain relies on balancing neuronal circuitry, and while changes to this system, such as the excitation-inhibition system, can result in numerous disorders, no drug exists that can help the body regulate these important circuits.
A vital compound has been developed which can aid in this needed homeostasis.
Significant neurological disorders; epilepsy, schizophrenia and autism, are not well treated by current medications. It is accepted that novel, game-changing, approaches are required. A commonality of these diseases is that they arise from pathological alteration to the excitation-inhibition balance of the brain. Moreover, it is probable that perturbation of this balance occurs during early nervous system development, which then becomes ‘locked-in’.
The excitation-balance of the brain is regulated and maintained by neuronal homeostasis. All neurons employ homeostatic mechanisms to manage excitability (i.e. to maintain circuit stability). Given its importance, neuronal homeostasis is a potentially very attractive drug target. However, no such drugs have been identified.
Researchers at The University of Manchester have developed a compound that increases expression of a key homeostatic regulator: Pumilio. As predicted, this compound is a potent anticonvulsant in mouse models of epilepsy (through restoration of the excitation-inhibition balance). This activity demonstrates the potential for manipulation of neuronal homeostasis. It is anticipated that development of this compound, and similar drugs, will have enormous clinical potential.
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