Autism affects approximately 2 percent of children in the U.S., with approximately 30 percent of these kids having seizures. Recent large-scale genetic study has identified genetic variations in a sodium channel called voltage-gated sodium channel Nav1.2 – a major cause of autism.
Seizures are caused by hyperactive sodium channels in the cell. Doctors frequently treat seizures by administering a drug that closes sodium channels, hence decreasing sodium flow through axons.
While this type of treatment is effective for the majority of patients, it is ineffective in up to 20 percent or 30 percent of cases. These youngsters carry Nav1.2 “loss-of-function” variants, which are likely to decrease sodium channel activation as an “anti-seizure” mechanism.
Thus, the mechanism by which a sodium channel Nav1.2 deficit results in seizures remains a big conundrum in the area, perplexing clinicians and scientists.
Yang Yang, an assistant professor of medicinal chemistry and molecular pharmacology at Purdue University, and his team, which included post-doctoral researcher Jingliang Zhang as the first author of the publication, took on the problem.
They discovered that in neurons lacking Nav1.2, the expression of a large number of potassium channels is significantly reduced. The Nav1.2 defect does not induce seizures; rather, the issue emerges when the potassium channels overcompensate for the sodium channel shortfall by shutting down an excessive number of potassium channels, causing the neuron to become hyperexcitable and resulting in seizures.
In such circumstances, it is evident that blocking the sodium channel is ineffective. Yang and his colleagues hypothesize that creating medications to activate potassium channels would aid in seizure control in these patients.
Notably, researchers led by Kevin Bender’s study group at the University of California, San Francisco independently made a similar observation. Yang and Bender’s papers were published concurrently in Cell Reports.
“We’re looking at genetic makeup, so doctors can prescribe a drug and gene therapy based on genes identified—personalized medicines,” Yang said.
“Our research points toward a direction for future research, maybe future treatments. We are peacetime warriors, fighting humanity’s biggest enemy: disease. There are kids dying because of these conditions. Our goal is to help them, to help their parents and their families. This kind of basic research is a vital part of finding new drugs.”
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