Fluoxetine Alleviates Core Autism Symptoms of SHANK3 Mutant Monkey

The prevalence of autism is 1% of the general population and there is currently no effective drug treatment. Scientists found recently short-term medication with fluoxetine can alleviate core symptoms of an autism monkey.

 

Mutations in the postsynaptic skeletal protein SHANK3 are the most common genetic cause of autism. Although mutant mice have contributed enormously to our current understanding of the pathophysiology of SHANK3-associated autism, the evolutionary differences in brain anatomy and behavior between mice and humans pose great challenge in using rodents to model autism.

 

In cooperation with professor Xiao-jiang Li from Emory University and Jinan University in Guangzhou, China, and professor Yong-hui Jiang from Duke University in the United States, the team led by Dr. ZHANG Yong Q. from the institute of Genetics and Developmental Biology of the Chinese Academy of Sciences successfully generated crab-eating monkeys carrying SHANK3 mutations using the latest CRISPR/Cas9 gene editing technology in 2017 (Zhao et al., Cell Research, 2017).

More recently, the three laboratories collaborated again on a systematic analysis of the SHANK3 mutant monkey behaviors. They found that the mutant monkey exhibited typical core symptoms of autism, including social communication impairment and stereotypical repetitive behaviors. Positron emission tomography (PET) detected a decreased metabolic activity in the mutant monkey brain. Subsequently, they found that the antidepressant fluoxetine was effective in relieving abnormal behaviors and brain metabolic activity in the mutant monkey.

 

“The generation of SHANK3 mutant monkey provides an important platform for development of autism drugs”, said ZHANG Yong Q.

 

A paper entitled “CRISPR/Cas9-mediated Disruption of SHANK3 in Monkey Leads to Drug-treatable Autism-like Symptoms” was recently published online in the journal Human Molecular Genetics.

 

 

 

Movie: SHANK3 mutant monkey before and after fluoxetine treatment. Fluoxetine, a selective serotonin reuptake inhibitor, was approved by FDA in 1987 to treat depression as well as anxiety and obsessive-compulsive disorder. The mutant monkey exhibited obvious stereotypical behaviors induced by external stimuli, indicating that the mutant monkey was in a state of stress and anxiety. After two weeks of continuous oral administration of fluoxetine, the mutant monkey became less anxious and began to socialize evidenced by grooming each other. (By IGDB)