Researchers have pinpointed a gene network in the brain that causes epilepsy when it is disrupted. Based on the results, they are predicting which drugs will work to restore the network’s function.
Epilepsy is a neurological disorder that causes recurring unprovoked seizures. The search for treatment is still ongoing and current research to identify new anti-epileptic drugs has been largely unsuccessful as the method of targeting genes—one at a time—to find suitable targets and develop drugs is ineffective and expensive.
For the new study, the team began by building gene networks expressed across the human brain with samples from healthy subjects. Following an analysis of a large database of mutations and genes associated with epilepsy, the researchers discovered a gene network associated with rare and common forms of epilepsy.
Known as M30, this epileptic-network contains 320 genes and represents a previously unknown mechanism which regulates susceptibility to epilepsy.
The researchers conducted analyses in mouse models of epilepsy, which suggested that the disruption of M30 contributed to the manifestation of epilepsy. The team confirmed their findings through computational approaches based on network-biology, leveraging public data resources to predict the effect of drugs and small molecules on the network to restore M30 to a healthy state.
The results, published in the journal Genome Biology, suggest that targeting M30 with a combination of drugs may be a viable strategy in treating epilepsy.
“Our approach allowed us to identify a network associated with epilepsy and provide a compelling proof-of-principle by predicting a known anti-epileptic drug to target the network,” says Enrico Petretto, an associate professor at Duke-NUS.
“We were able to do this in a matter of few months only using publicly available data, while a typical effort to identify anti-epileptic drugs would usually take years.”
Petretto conducted the work in collaboration with researchers at Imperial College London.
Source: National University of Singapore