Researchers Find Enzyme Linked to Autistic Behavior

A new study finds that an enzyme - MMP-9 - plays an important role in the development of autistic behavior in people with Fragile X Syndrome.

The study, conducted by researchers at the University of California, Riverside, shows that enzymes might be involved in autistic symptoms. Researchers used mice models in the study. 

Fragile X syndrome is a genetic condition that causes developmental problems. The disorder is more common in boys than in girls.

Brain cells produce MMP-9. During its inactive state, it is secreted into spaces between brain cells. Healthy people have a lot of the enzyme in the brain. Activation of even a small amount of MMP-9 leads to significant changes in neuronal connections. Higher activation of the enzyme leads to unstable connections in brain cells in people with FXS.

"Our study targets MMP-9 as a potential therapeutic target in Fragile X and shows that genetic deletion of MMP-9 favorably impacts key aspects of FXS-associated anatomical alterations and behaviors in a mouse model of Fragile X," said Iryna Ethell, a professor of biomedical sciences in the UC Riverside School of Medicine, who co-led the study, according to a news release. "We found that too much MMP-9 activity causes synapses to become unstable, which leads to functional deficits that depend on where in the brain that occurs."

Ethell and colleagues have previously shown that FMR1 gene is associated with FXS. However, researchers didn't know how these mutations cause unstable synapses. The present study shows that MMP-9 inhibitor, minocycline can reduce some behavioural aspect of FXS. Researchers even say that some day it might be possible to treat FXS using an inhibitor that suppresses MMP-9 activity.

Researchers conducted the present study on mice models that lacked FMR1 and MMP-9. They found that mice with mutations in FMR1 displayed autistic behavior and macroorchidism (abnormally large testes). Mice with no MMP-9 had no autistic symptoms.

"Our work points directly to MMP-9 over-activation as a cause for synaptic irregularities in FXS, with potential implications for other autistic spectrum disorders and perhaps Alzheimer's disease," said Doug Ethell, the head of Molecular Neurobiology at the Western University of Health Sciences, Pomona, Calif., and a co-author of the study.

The study is published in the Journal of Neuroscience.