Dane M. Chetkovich, M.D., Ph.D., Neurology at Northwestern University, is working on a gene therapy treatment for epilepsy that may one day help patients who are otherwise resistant to medical and surgical therapy.

With his 2009 BRF Seed Grant, Dr. Chetkovich generated enough data early on that allowed him to submit a grant proposal to NIH. In 2010, he was awarded an R21 (an exploratory/developmental research grant provided by NIH) in the amount of $275,000.

Epilepsy is a brain disorder of abnormally increased brain excitability that leads to seizures. A person is considered to have epilepsy when he or she has two or more unprovoked seizures. Advances in therapeutics have improved the lives of patients with epilepsy, yet seizures refractory to medical intervention remain a significant cause of disability. Additionally, many of the patients who do achieve acceptable control of seizures with anti-epilepsy drugs suffer side-effects from multidrug combinations or high dosages, and may still develop drug resistance. Surgical removal of seizure-producing areas of the brain can control seizures in some patients, but is less effective in others. Thus, although substantial strides have been made in treating epilepsy, new therapies are warranted to help the many patients who suffer intractable seizures or complications from medical or surgical treatment efforts. Dr. Dane M. Chetkovich used his 2009 BRF Seed Grant to attempt to develop new epilepsy treatments to better the lives of these patients. 

The abnormal brain excitability that causes seizures often results from genetic or acquired deficiencies in ion channels that control neuronal excitability. Ion channels are proteins that form a pore across the plasma membrane of cells. In neurons, these channels help regulate the electrical activity by controlling the flow of ions across the membrane. When the regulation is disrupted, leading to a seizure, neurons may fire, or send signals on to other neurons in patterns that are very different from normal. 

Dr. Chetkovich focused on a likely candidate for explaining abnormalities of excitability in both hereditary and acquired epilepsy—the hyperpolarization-activated cyclic nucleotidegated (HCN) channel (h-channel). The h-channel family of ion channels consists of four different genes, HCN1-4, and has been implicated in epilepsy in animals and human patients. Dr. Chetkovich’s project examined whether using engineered viruses to produce HCN2 in abnormal areas of epileptic brain can stop seizures. These experiments aimed to develop and test techniques for viral gene therapy in an animal model of epilepsy with the ultimate goal of translating these techniques to patients with intractable epilepsy.

Other Successes

Aimee Kao, M.D., Ph.D.
BRF Accelerates a Lab and Career
Dr. Aimee Kao generates human cell lines to model neurodegenerative disorders The BRF Seed Grant was crucial in establishing us as a lab that is leading the work on neuroregeneration…
Ravi Allada, M.D.
Sleep Disorders and Neurodegenerative Diseases
Ravi Allada, M.D., Professor of Neurobiology at Northwestern University, is interested in the molecular mechanisms underlying circadian rhythms and their links to various clinical disorders, including insomnia, depression and even…
Dr. Krishnan, Ph.D.
High Impact
“The BRF Scientific Innovations Award allowed us to do bold, transformative work for which there was no precedent. I am grateful that BRF takes risks on innovation.”
Dr. Nicholas Hatsopoulos
From the Lab to the Patient
In 2002 Dr. Nicholas Hatsopoulos, Department of Organismal Biology and Anatomy at The University of Chicago, was awarded his first $25,000 seed grant. His lab set out to understand the…