A Promising Finding to Combat Autism

Promising Finding to Combat Autism

San Diego, CA


A group of researchers at Scintillon Institute in San Diego, California demonstrated a promising therapeutic intervention for autism in an animal model.  This study, published today in Nature Communications under the title of “NitroSynapsin therapy for a mouse MEF2C haploinsufficiency model of human autism”, proposes a therapeutic strategy to mitigate the hallmarks of MEF2C haploinsufficiency syndrome (MCHS), a condition where patients who carry one copy of defective MEF2C gene suffer from severe neurological conditions including autism spectrum disorders, intellectual disabilities, and seizures.  Fig-4f-crop-(002).jpg

Neurons of normal versus mutant cells


     “This work presents very important data showing how the knowledge about MEF2C’s functions may lead to treatment for autism. Such knowledge came from many years of research by Dr. Lipton’s group and others,” said the paper’s senior author Dr. Nobuki Nakanishi, a professor at Scintillon. 

     MEF2C is an activity-dependent transcription factor which is expressed in the brain, heart, and lymphocytes, both during development and in adulthood.  Dr. Stuart Lipton, who is a co-author of the paper, and his colleagues made seminal discoveries that established the notion that MEF2 transcription factors, including MEF2C, are prominent regulators of neuronal differentiation and survival in the brain. More recently, their work led to the recognition of MCHS as a genetic condition.

In the current study, the Scintillon team studied MEF2C-heterozygous (Mef2c-het) mice, in which one of two copies of the MEF2C gene was experimentally deleted, in their effort to establish an animal model of MCHS. They first observed that Mef2c-het mice exhibit behavioral deficits resembling those of human patients, including abnormal social behaviors, deficient learning and memory, and repetitive motor behaviors. Further analysis showed changes in genes associated with neurogenesis, synapse formation, and neuronal cell death with an increased ratio of excitatory to inhibitory (E/I) neurotransmission also observed. An increased E/I ratio emerged as one of the commonly observed phenotypes in various mouse models of autism and may explain the high prevalence of seizures among patients with autism. Most importantly, neurobehavioral deficits, E/I imbalance, and histological damage are all ameliorated by treatment with NitroSynapsin, a new experimental drug related to the FDA-approved drug memantine developed by Dr. Lipton.

In summary, the new study, with Dr. Shichun Tu at Scintillon as the first author, shows that MEF2C haploinsufficiency in mice leads to abnormal brain development, E/I imbalance, and neurobehavioral dysfunction, which may be mitigated by pharmacological intervention. These results may have implications for the treatment of human MCHS and other forms of autism spectrum disorders and intellectual disabilities. 

Other participating coauthors of the paper include scientists from the Scintillon Institute (Mohd Waseem Akhtar, James Parker, Kevin Lopez, Abdullah Sultan, Scott R. McKercher, and Rajesh Ambasudhan), the Sanford Burnham Prebys Medical Discovery Institute (Rosa Maria Escorihuela, Alejandro Amador-Arjona, Jeffrey D. Zaremba, Timothy Holland, Neha Bansal, Daniel R. Holohan, Scott D. Ryan, Shing Fai Chan, Li Yan, Xiaofei Zhang, Xiayu Huang, Huaxi Xu, and Alexey V. Terskikh), the University of California, Los Angeles (Vivek Swarup and Daniel H. Geschwind), Jinan University, China (Yuqiang Wang), the Scripps Research Institute (Amanda J. Roberts), and the University of California, San Diego (Robert A. Rissman and Eliezer Masliah).

Click here to read more: http://go.nature.com/2igyPkp


Rhianna Basore

858-799-1065 Outreach Coordinator

Scintillon Institute

6868 Nancy Ridge Drive San Diego CA 92121

[email protected]


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