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                  Treating neurological symptoms of CHARGE syndrome

                  by Editor
                  April 28, 2021
                  in Science
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                  Treating neurological symptoms of CHARGE syndrome
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                  IMAGE: INRS Professor Kessen Patten specializes in genetics and neurodegenerative diseases.
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                  Credit: Christian Fleury (INRS)

                  CHARGE syndrome is a rare genetic disorder affecting about 1 in 10,000 newborns. It can lead to neurological and behavioural disorders for which no treatment is currently available. Dr. Kessen Patten and his team, from the Institut national de la recherche scientifique (INRS) have just discovered a compound that could alleviate these symptoms. The results of their research were published in the journal EMBO Reports.

                  Understanding Neurological Disorders

                  First described in 1979, CHARGE syndrome is caused by mutations in the CHD7 gene and is associated with neurodevelopmental disorders such as intellectual disability, attention deficit disorder with or without hyperactivity, seizures and autism spectrum disorder. Dr. Patten’s research team studied the neurological symptoms of this syndrome, which are still poorly understood.

                  The team developed a genetic model of zebrafish with loss of function of the CHD7 gene similar to that observed in humans. They found that the CHD7 gene regulated the type of GABAergic neurons that are essential for proper brain function.

                  “The loss of function of CHD7 appears to cause developmental and functional abnormalities in GABAergic neurons in the zebrafish brain that are related to the observed neurological and behavioural disorders,” explained Dr. Patten, who specializes in genetics and neurodegenerative diseases. The team also identified molecular events controlled by the CHD7 gene to explain these neurological symptoms in their genetic model. Similar findings were made using cells from patients with the disease.

                  Finding a Drug

                  The research team tested hundreds of compounds already approved for clinical use by the U.S. Food and Drug Administration. Drug screening was used to identify potential candidates for treatment–ephedrine was selected as the most therapeutic compound. “We observed therapeutic effects on both, the neurological and behavioural symptoms,” said PhD student Priyanka Jamadagni, lead author of the article. “It allowed the diseased zebrafish model to partially recover its normal functions.”

                  This research opens the door to new avenues for the treatment of other neurological disorders with similar neuronal imbalances, such as autism spectrum disorder and hyperactivity.

                  ###

                  About the study

                  The article “Chromatin remodeler CHD7 is required for GABAergic neuron development by promoting PAQR3 expression,” by Priyanka Jamadagni, Maximilian Breuer, Kathrin Schmeisser, Tatiana Cardinal, Betelhem Kassa, J Alex Parker, Nicolas Pilon, Eric Samarut, and Shunmoogum A. Patten, was published in the journal EMBO Reports. Led by Dr. Patten, the study was conducted with the help of collaborators from the CHUM Research Centre and Université de Québec à Montréal (UQAM). The study received financial support from the CHARGE Syndrome Foundation, the Canada Foundation for Innovation (CFI), the Natural Sciences and Engineering Research Council of Canada (NSERC), and the Rare Disease Foundation. The lead author holds a doctoral scholarship from the Center of Excellence in Research on Orphan Diseases – Courtois Foundation (CERMO-FC) and a scholarship from the Armand-Frappier Foundation.

                  About INRS

                  INRS is a university dedicated exclusively to graduate level research and training. Since its creation in 1969, INRS has played an active role in Quebec’s economic, social, and cultural development and is ranked first for research intensity in Quebec and in Canada. INRS is made up of four interdisciplinary research and training centres in Quebec City, Montreal, Laval, and Varennes, with expertise in strategic sectors: Eau Terre Environnement, Énergie Matériaux Télécommunications, Urbanisation Culture Société, and Armand-Frappier Santé Biotechnologie. The INRS community includes more than 1,500 students, postdoctoral fellows, faculty members, and staff.

                  Source :

                  Audrey-Maude Vézina

                  Service des communications de l’INRS

                  418 254-2156

                  audrey-maude.vezina@inrs.ca

                  Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.



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