A gene network in the brain, called M30, that causes epilepsy when it is disrupted has been identified by researchers at Duke-National University of Singapore Medical School. They are predicting, based on the results, 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 this 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.
Gene Network M30
Known as M30, this epileptic-network contains 320 genes and represents a previously unknown mechanism which regulates susceptibility to epilepsy.
Researchers conducted analyses in mouse models of epilepsy, which suggested that the disruption of M30 contributed to the manifestation of epilepsy. Findings were confirmed 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.
Enrico Petretto, an associate professor at Duke-NUS, said:
“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. 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.”
Funding for the work was provided by the European Union’s Seventh Framework Program, Marie Curie Actions, Intra-European Fellowships for Career Development, UK Imperial National Institute for Health Research Biomedical Research Centre, the UK Medical Research Council, UCB Pharma, Duke-National University of Singapore (NUS) Medical School and the Singapore Ministry of Health (EP).
Andree Delahaye-Durie, Prashant Srivastava, Kirill Shkura, Sarah R. Langley, Liisi Laaniste, Aida Moreno-Moral, Bénédicte Danis, Manuela Mazzuferi, Patrik Foerch, Elena V. Gazina, Kay Richards, Steven Petrou, Rafal M. Kaminski, Enrico Petretto and Michael R. Johnson
Rare and common epilepsies converge on a shared gene regulatory network providing opportunities for novel antiepileptic drug discovery
Genome Biology 201617:245 DOI: 10.1186/s13059-016-1097-7