In this project, Dr. Sahara Khademullah will establish whether a protein called KCC2 (potassium chloride cotransporter 2), which is found to be lower in people with sporadic ALS than in people without the disease, is a viable target to prevent or stop ALS progression. Dr. Khademullah will determine the extent of KCC2 deficits and when they occur in mice that have been genetically altered to mimic aspects of human ALS. Using newly-developed and non-invasive technology, she will also measure a readout of KCC2 loss in real time as the disease progresses in mice.
Dr. Khademullah will also determine whether KCC2 in cerebrospinal fluid (CSF) could be a reliable biomarker for ALS. She will collect CSF from ALS mice before they have developed symptoms and throughout disease onset and progression and compare the results to CSF from normal mice. Learning when KCC2 deficits occur may provide essential clues about optimal timing for treatment. Finally, Dr. Khademullah will test whether an experimental drug developed by Dr. De Koninck called CLP290 can retain or recover the ability to inhibit motor neurons by restoring KCC2 levels, which may slow or even stop disease progression. Overall, this research may identify KCC2 as a viable target for future drug development and a reliable biomarker to speed diagnosis and measure responses to new treatment options in clinical trials.