The cure for the most commonly fatal cause of catastrophic infant epilepsy, a condition with devastating developmental effects in children, could come from the venom of a tarantula and two scientists' chance conversation.
Dravet syndrome most commonly occurs when only one version of a child’s two copies of the SCN1A gene works properly. Children with this condition produce half the required quantity of NaV1.1 protein, leading to multiple seizures a day. These, in turn, cause intellectual disabilities and often early death.
Professor Steven Petrou of the Florey Institute of Neuroscience and Mental Health, told IFLScience some researchers are exploring the possibility of fixing the malfunctioning gene, or supplementing NaV1.1, but his team has a different approach.
“We reasoned that if we could just make the remaining protein work harder, it would effectively pick up the slack – much like a cyclist on a tandem bicycle can help her exhausted passenger by pedaling harder to maintain speed,” Petrou said in a statement.
Petrou was thinking about the characteristics a molecule would need to affect SCN1A in this way, when he had a conversation with Professor Glenn King of the University of Queensland, an expert on the composition of venoms. Petrou mentioned what he needed to King, who told him he might have just the thing in the venom of a West African tarantula (Heteroscodra maculata).
Their trials of the Hm1a molecule on mice with Dravet syndrome, reported in Proceedings of the National Academy of Sciences, have been stunningly successful. The portion of the brain responsible for dampening excessive activity elsewhere started off suppressed, and the mice suffered numerous seizures as a result.
“After applying the compound from the spider venom to nerve cells from the brains of Dravet mice we saw their activity immediately return to normal,” Petrou said. ”Infusion into the brains of the Dravet mice not only restored normal brain function within minutes but over three days, we noted a dramatic reduction in seizures in the mice and increased survival. Every single untreated mouse died.”
Of course, not all medications that work in rodents transfer successfully to humans, but the findings could certainly bring hope to families of 10,000-20,000 Dravet sufferers worldwide.
The medication that will eventually be used in clinical trials will almost certainly not be the exact tarantula molecule. Petrou explained that while tarantula venom has been evolutionarily honed for bioactivity, it has not been optimized for treating Dravet. The molecule in question has a half-life of only 1-2 hours and cannot cross the blood-brain barrier.
To avoid the need for frequent injections into the cerebrospinal fluid, Petrou will need to find a way to improve on what the tarantulas produce. The successful proof of concept should make it much easier to get the support to keep searching.