Targeting chloride for neurological disease
Nature Medicine
October 7, 2013
The activity of the potassium-chloride membrane protein, KCC2, is reduced in many neurological and psychiatric disorders in humans, such as chronic pain, anxiety, and epilepsy. A study published online this week in Nature Medicine reports a newly-developed small molecule that can activate KCC2 and reduce chronic pain in rats. The findings suggest a promising therapeutic approach to treat pain and other conditions in which the KCC2 activity is impaired.
KCC2 is a transmembrane pump that keeps chloride ion concentrations low within neurons, which enables inhibition of nerve impulses. Therefore, Yves De Koninck and colleagues reason that a drug that could activate KCC2 may prove promising in the clinic to restore inhibitory signals and treat neurological diseases. The team screened a small molecule compound library and identify a drug, which they call CLP257. They go on to show that this drug can enhance KCC2 expression and its activity and reduce pain in rats with nerve injury.
They note that a related compound with better pharmacological profiles than CLP257 was as effective in reducing pain in rats as an existing pain treatment called pregabalin, but it lacked the undesirable motor side effects that are often seen with that drug.
doi: 10.1038/nm.3356
Research highlights
-
Jun 24
Palaeontology: It sucked to be the prey of ancient cephalopodsScientific Reports
-
Jun 24
Sport science: New wearable sensor to measure neck strain may detect potential concussionScientific Reports
-
Jun 23
Scientific community: Women credited less than men in scientific paper authorshipNature
-
Jun 17
Health technology: New cost-effective smartphone test for middle ear functionCommunications Medicine
-
Jun 17
Conservation: Feral cats pushing critically endangered marsupial further towards extinctionScientific Reports
-
Jun 16
Microbiology: DNA analysis indicates origins of the Black DeathNature