Medical Research and Developments


New Research Offers Hope For Novel Treatments For AHC
In a new peer-reviewed research article published March 20, 2013 by the School of Biomedical Sciences, University of Leeds in the United Kingdom entitled "Alternating Hemiplegia of Childhood-Related Neural and Behavioural Phenotypes in Na+,K+-ATPase α3 Missense Mutant Mice", possible hope for novel treatments for Alternating Hemiplegia of Childhood (AHC) were set out. Duke Children’s Hospital Professor of Pediatrics and Professor of Neurobiology, Dr. M. Makati submitted to our colleagues in the US a summary of the results of the study. Read a summary of the results below.

M. Mikati, MD - On Recent Research
Researchers in the School of Biomedical Sciences, University of Leeds in the United Kingdom recently reported the effects of a specific type of mutation in the ATP1A3 gene (a Missense mutation that causes complete loss of function of the protein coded in that gene) in a mouse that carries that mutation (called the Myshkin mouse). Other types of mutations that cause altered but not complete loss of function in the ATP1A3 gene are known to cause AHC in children affected with this disorder.

First the investigators analyzed the mutation of the Myshkin mouse using computer based modeling and predicted that the mutation should have effects similar to those that mutations seen in AHC patients have. Then they tested this mouse in the laboratory and observed motor control dysfunction and cognitive impairments that are somewhat similar to what patients with AHC manifest. Using neuroimaging techniques they also showed that the frontal part of this mouse’ brain is not well connected to the rest of the brain, which is another similarity to what has been observed in children with AHC.

This study provides a mouse model that has similarities to the human condition of AHC. Use of this mouse model or of ones under development that have the same mutations seen in children with AHC could help better understand the underlying pathophysiology of AHC and to screen for medications to treat this condition.

Duke University Announces Mouse Model of AHC mutation of ATP1A3:
It was recently discovered at Duke, through an international collaborative effort, that AHC is due to mutations in the gene coding for a cell surface protein called ATPase1a3. This protein is known to be important for the normal functioning of brain cells, but how the mutations lead to abnormal function of the brain and to AHC is not yet known. Also, there is no effective therapy of AHC yet. Duke's research will study, in a mouse model that they developed carrying the most common mutation seen in the AHC human cases, the characteristics as well as the underlying electrochemical physiology of this mutation in the hope of understanding the underlying mechanisms leading to AHC symptoms and to eventually developing better therapeutic strategies for AHC and related disorders.

Duke announced at the recent symposia in Washington DC that they had begun their research into identifing drugs or drug-like compounds that are capable of restoring normal ATP1A3 gene function in their mouse models.

Vanderbilt and Northwestern Univerties

Dr. Kevin Ess at Vanderbilt University and Dr. Alfred George, Jr. at Northwestern University are doing work to determine the functional and biochemical consequences of the three most common gene mutations causing AHC. They will also continue to identify drugs or drug-like compounds through a drug screening program that are capable of restoring normal ATP1A3 gene function. Finally, they have made induced pluripotent stem cells (iPSCs) derived from AHC patients.  These again include the three most common gene mutations causing AHC.  These patient derived stem cells will be used to investigate electrophysiological abnormalities of neurons and to test whether compounds they have identified can restore ATP1A3 function.

French Study

A study in being carried out in France with the help of the Frecnh family association to identify whether a special diet complimented by a particular oil supplement can reduce the frequency and duration of AHC episodes in young adults with the condition.

International Research Consortium Working on Genotype/Phenotype:
Currently an International consortium of investigators that is based on the collaboration that lead to the gene discovery a year ago is performing a study to correlate the type of mutations in the ATP1A3 gene with the clinical symptoms and manifestations of the disease. The goal is to determine if the type of mutation can predict the severity and type of symptoms that patients with AHC manifest.

Funding for research into this rare condition is always required.