A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Fall, 2017 | Number 4, Volume 31

Drug affecting gene linked to autism shows possible usefulness in animal tests

Animal research suggests that a new drug called NitroSynapsin, which affects the function of a gene called MEF2C, may potentially be useful in treating autism. 

In 1993, Stuart Lipton and colleagues found that MEF2C plays a key role in brain development. In addition, the researchers discovered that disrupting this gene in the brains of mice early in fetal development leads to severe, autism-like abnormalities. Since that time, other researchers have identified a similar disorder—now known as MEF2C haploinsufficiency syndrome, or MHS—in a number of children with autism. 

While only a small percentage of cases of autism involve MHS, genomic research has shown that mutations underlying autism often involve genes whose activity is switched on by MEF2C. Thus, Lipton says, “we’re hopeful that a treatment that works for this MEF2Chaploinsufficiency syndrome will also be effective against other forms of autism, and in fact, we already have preliminary evidence for this.” 

The researchers created a mouse model of MHS by deleting one copy of the mouse variant of MEF2C. The altered mice displayed impaired spatial memory, abnormal anxiety, abnormal repetitive movements, and other signs resembling human MHS. The brains of the mice exhibited an increase in excitatory as compared to inhibitory signaling—a common finding in humans with autism as well. 

The researchers treated the mice with NitroSynapsin, a drug related to the Alzheimer’s drug memantine, for three months. They report that the drug helped to reduce the excitatory/inhibitory imbalance in the brains of the mice, as well as reducing abnormal behaviors and boosting the animals’ performance on cognitive and behavioral tests. 

The researchers are currently testing the drug on a cell-based model of MHS using skin cells from children with the syndrome, and report that it appears to be effective in this model as well. 


“NitroSynapsin therapy for a mouse MEF2C haploinsufficiency model of human autism,” Shichun Tu, Mohd Waseem Akhtar, Rosa Maria Escorihuela, Alejandro Amador-Arjona, Vivek Swarup, James Parker, Jeffrey D. Zaremba, Timothy Holland, Neha Bansal, Daniel R. Holohan, Kevin Lopez, Scott D. Ryan, Shing Fai Chan, Li Yan, Xiaofei Zhang, Xiayu Huang, Abdullah Sultan, Scott R. McKercher, Rajesh Ambasudhan, Huaxi Xu, Yuqiang Wang, Daniel H. Geschwind, Amanda J. Roberts, Alexey V. Terskikh, Robert A. Rissman, Eliezer Masliah, Stuart A. Lipton, and Nobuki Nakanishi, Nature Communications, November 14, 2017 (free online). Address: Shichun Tu, Neuroscience and Aging Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, [email protected]


“New autism drug shows promise in preclinical study,” GEN News Highlights, November 14, 2017.