Examining the role of KCC2 in maintaining the balance between excitation and inhibition in ALS

Researchers have found that before the onset of ALS there is an increase in the activity of motor neurons in the spinal cord. One theory about why this happens is that there is a decrease in KCC2, a protein that’s responsible for keeping hyperactivity in check by maintaining the right amount of chloride, a chemical that plays a role in activating neurons. Researchers have identified that people with the sporadic form of ALS have lower amounts of KCC2. Dr. De Koninck has developed two promising drugs that can increase KCC2 production. In this project, he will use ALS laboratory mice to test whether restoring KCC2 levels with these drugs – whether in upper motor neurons that originate in the brain, lower motor neurons that originate in the spinal cord, or both – can prevent neurodegeneration and motor deficits. Dr. De Koninck will also investigate whether measuring KCC2 in spinal fluid can be used as a biomarker to diagnose ALS before symptom onset. Altogether, this project has the potential to help us better understand, diagnose and treat ALS.