Enzyme Linked to Autistic Behavior in Fragile X Syndrome

Scientists have long struggled with linking a more direct culprit to autism--a developmental disorder that's estimated to affect close to 1.5 million Americans. Yet a recent study conducted by researchers at the University of California, Riverside, found that certain enzymes may be connected to the issue.

Findings published in the Journal of Neuroscience showed that the enzyme MMP-9 plays an important role in the development of certain autistic behaviors--specifically in patients with Fragile X Syndrome.

"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, in 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."

In otherwise healthy individuals, the brain cells produce inactive MMP-9; the activation of even small amounts can carry a great effect on connections between synapses. However, too much MMP-9 activity can lead to unstable problems that may ultimately cause functional deficits commonly seem in autism.

Though researchers were previously unaware how certain mutations, such as FMR1 and MMP-9, resulted in unstable changes, the present findings explore how the MMP-9 inhibitor, minoclycline, can reduce some behavioral aspects of FXS. Furthermore, researchers said they believe that it may one day be possible to treat FXS with an inhibitor that suppresses MMP-9 activity.

Researchers conducted the present study on mice models that tracked both FMR1 and MMP-9. They discovered that mice with mutations in FMR1 showed signs of autistic behaviors and abnormally large testes. Those with no MMP-9, however, did not.

"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 co-author of the study Doug Ethell, the head of Molecular Neurobiology at the Western University of Health Sciences, Pomona, Calif.

With future studies, researchers hope to determine the strength of synapse stability inside the neurons regulated by MMP-9.