Project Grant R21NS150783

The National Institute of Neurological Disorders and Stroke awarded Northwestern University $440,000 on August 15, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853) to characterize disease-associated KCNH1 mutations in human neurons.

The research establishes cellular and molecular mechanisms by which heterozygous KCNH1 variants cause Templebaraitser Syndrome and Zimmermannlaband Syndrome, rare neurodevelopmental disorders marked by developmental delay, facial and digital abnormalities, and epileptic seizures. The project uses ion channel biology, CRISPR/Cas9 gene editing, and induced pluripotent stem cell technologies to perform systematic characterization of KCNH1 mutations in human iPSC-derived excitatory and inhibitory neurons, including evaluation of antisense oligonucleotide treatments as a potential therapeutic approach to reverse gain-of-function defects in neuronal excitability.

The award is classified as a Project Grant. Work is performed in Chicago, Illinois. The period of performance runs from August 15, 2026, through July 31, 2028. The project grant mechanism supports exploratory research to establish proof-of-concept for novel therapeutic strategies targeting ion channel dysfunction in rare neurological disease, addressing a gap in disease-modifying therapies where selective small-molecule approaches face significant off-target safety challenges.