Could a tuberculosis drug help treat autism?

An antibiotic used to treat tuberculosis has the potential to alleviate the social impairments associated with autism spectrum disorder, new research suggests.

 
The study reveals that the drug d-cycloserine boosted the function of an autism-related gene called PCDH10 and improved social impairments in mice.
Senior study author Prof. Edward Brodkin, of the University of Pennsylvania, and colleagues recently reported their findings in the journal Biological Psychiatry.
Autism spectrum disorder (ASD) is a developmental disorder characterized by problems with social skills, communication, and behavior.
The Centers for Disease Control and Prevention (CDC) estimate that around 1 in 68 children in the United States have ASD, and the condition is around 4.5 times more common among boys than girls.
While the exact causes of autism are unclear, studies have suggested that genetics may play a role. One gene that has been associated with the condition is PCDH10.
According to Prof. Brodkin and colleagues, PCDH10 is expressed in the amygdala – a brain region that has been linked to social and behavioral impairments in people with autism. However, precisely how this gene affects neuronal activity in the amygdala to influence social behavior remains unknown.

PCDH10 reduces NMDA glutamate receptor subunit levels

For their study, the researchers set out to gain a better understanding of the role of PCDH10 in autism-related social deficits.
First, the team analyzed the neurons in the amygdala of mice that were genetically engineered to lack one copy of the PCDH10 gene, reducing its function.
The researchers found that these neurons showed a reduction in NMDA glutamate receptor subunit levels, which is an indicator of disrupted connectivity in neural circuits.
Furthermore, the rodents displayed social deficits, further confirming the role of PCDH10 in social behavior.
Interestingly, the social behavior of male mice was more affected by reduced PCDH10 function than that of female mice, which correlates with the higher incidence of ASD in male humans.

Next, the researchers treated the mice with d-cycloserine (brand name Seromycin), an antibiotic prescribed for the treatment of tuberculosis and urinary tract infections.
The team explains that d-cycloserine is known to boost NMDA glutamate receptor function, and previous studies have suggested that the drug may be effective for the treatment of anxiety disorders.
Following treatment with d-cycloserine, the researchers identified an improvement in social impairments among the rodents.
Not only does this study shed light on the mechanisms by which PCDH10 contributes to social deficits in ASD, but it also points to a potential treatment for such impairments.
However, Prof. Brodkin notes that much more research is required in both animals and humans before d-cycloserine can be recommended as a safe and effective treatment for ASD.