Grants bolster research on rare neurological disorder AHC

Kevin Ess, M.D., Ph.D., Gerald M. Fenichel Professor of Neurology, has received two grants from the Alternating Hemiplegia of Childhood Foundation (AHCF).

Kevin C. Ess, MD,PhD

Kevin Ess, M.D., Ph.D.
The grants will support efforts to understand cellular and molecular defects that contribute to AHC, a rare neurological disorder that causes repeated, sporadic attacks of hemiplegia — paralysis of part of the body. Patients with AHC often also suffer developmental delay, epilepsy and dystonia (abnormal muscle tone).

The hemiplegia attacks in AHC may cause mild weakness to complete paralysis on one or both sides of the body — sometimes alternating between sides — and they can vary in duration from minutes to hours to days. Patients are usually diagnosed before 18 months of age and may initially be misdiagnosed as having a seizure disorder instead of hemiplegia.

In up to 75 percent of patients, mutations in the gene ATP1A3 cause the disease. ATP1A3 encodes a protein component of the sodium/potassium ATPase — a molecular pump that moves sodium and potassium ions across the cell membrane and is responsible for establishing and maintaining the electrical gradients that are important for nerve and muscle excitability.

In a project that AHCF has continuously supported since 2012, Ess and close collaborator Alfred George, M.D., at Northwestern University, are studying human neurons generated from AHC patient-derived stem cells.

They are also using gene editing approaches to correct the ATP1A3 mutations in patient-derived cells. In addition, they are screening drugs and compounds for their ability to correct the defect in order to identify potential new treatments for AHC.

Ess also received AHCF funding for a second complementary project, in which his team is generating specific antibodies directed against the alpha3 and alpha2 subunits of the sodium/potassium ATPase. These antibodies will be highly useful tools for assessing levels of the specific subunits of the sodium/potassium ATPase.

They will be used not only in the human stem cell-based models, but also in mouse models of AHC that are being developed, Ess said.

“This should be an excellent investment that should continue to pay dividends far into the future,” Ess added.

Ess is the director of the Division of Pediatric Neurology and leads an AHC clinic at Monroe Carell Jr. Children’s Hospital at Vanderbilt.

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