In a 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, offers hope for novel treatments for Alternating Hemiplegia of Childhood (AHC). Duke Children’s Hospital Professor of Pediatrics and Professor of Neurobiology, Dr. M. Makati submitted to Cure AHC a summary of the results of the study. Read the full study here.
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 patient.. 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 a to screen for medications to treat this condition.
Duke University Announces Mouse Model of AHC mutation of ATP1A3 :
Alternating Hemiplegia of Childhood (AHC) is a severe disorder that causes episodes of paralysis, severe muscle contractions, epileptic seizures and developmental delay. 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. Our research will study, in a mouse model that we 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.
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