Rare Disease Report

Vanderbilt and Northwestern Researchers Receive AHCF Grants

JULY 17, 2017
Getting us one step closer - The AHC Foundation continues it’s commitment to find a treatment and a cure for AHC by funding major research projects!
Vanderbilt/Northwestern Phase “6”
The Alternating Hemiplegia of Childhood Foundation (AHCF), is pleased to announce an award of  $132,535.00 to the Department of Pharmacology, Northwestern University, Feinberg School of Medicine with Alfred George, M.D., as primary investigator, plus an award of $115,135.00 to the Division of Pediatric Neurology, Department of Medicine, Vanderbilt University School of Medicine with Dr Kevin Ess as primary investigator.

They will be working together on the project “Molecular Physiology and Pharmacology of ATP1A3 Mutations in AHC” known as “phase six”. The period of support is July 1, 2017 to June 30, 2018 and totals $247,670.00.
This project will continue investigating the cellular and molecular defects in AHC by studying human neurons generated from patient-derived stem cells coupled with pharmacological strategies to correct the defect. The team will also use gene editing to correct ATP1A3 mutations in patient-derived stem cells and create a ‘knock-out’ stem cell line useful for investigating AHC causing mechanisms.
The investigators have made great progress identifying a central electrophysiological deficit in AHC neurons carrying the G947R mutation and are now turning attention to studying neurons with other common and less common mutations. In addition, the team is testing drugs and compounds for their ability to rescue the primary cellular defect as a first step toward identifying new potential treatments for AHC.
Antibody Acceleration Project
AHCF also has funded an acceleration project in the amount of $62,237 awarded to  Kevin Ess, M.D., Ph.D., and his team at Vanderbilt to generate and validate highly specific antibodies targeted against the alpha 3 and alpha 2 subunits of the Na/K ATPase.

Dr Ess says: 

“Such tools will greatly accelerate our research as we will be able to be accurately assess levels of these important proteins. We expect them to not only work for our human stem cell based models of AHC but given the extremely high sequence homology, to also be useful for mouse models of AHC/RDP/CAPOS as well.

"As the antibodies we will make are monoclonal and derived from immortal cell lines, we expect to generate unlimited and eventually very inexpensive antibodies. As we will share these tools with other scientists throughout the world, this should be an excellent investment that should continue to pay dividends far into the future.”
Mouse Models
In addition to the above grants, AHCF is in the halfway point of a grant which implements two different mouse models of AHC caused by distinct ATP1A3 mutations (D801Y, G947R) to enable basic investigations of this disease. These mouse models will be used to test the effectiveness of various approved drugs and experimental compounds to alleviate symptoms of the disease; and 2) to identify genetic factors other than the primary ATP1A3 mutation that influences severity of symptoms (hemiplegia, dystonia) as well as the propensity for epilepsy.

The findings will contribute to the discovery of better pharmacological treatments for AHC and reveal new disease mechanisms that could be exploited for novel therapeutic strategies.
If you are an interested researcher with a project for AHC please contact Sharon@ahckids.org

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