Dopamine-disrupting topical cream could stop parasitic worms from getting under your skin

Threadworms, which are a type of parasitic nematode, spend a lot of time crawling around on human skin, poking and prodding to find the best place for entry before burrowing in. But disrupting a particular dopamine-sensing pathway causes them to lose interest, UCLA neurobiologists said in a paper published in Nature Communications.

In humans, dopamine is associated with pleasure and reward. In parasitic worms, the same molecule is associated with the drive to penetrate skin. Without dopamine signaling, the worms still crawl on the skin’s surface but rarely attempt to burrow into the skin. The researchers believe a topical preparation that disrupts this dopamine pathway could prevent infection and be used similarly to the way that DEET mosquito sprays prevent mosquito bites.

Globally, over 600 million people are infected with the skin-penetrating threadworm, Strongyloides stercoralis, mostly in tropical and subtropical regions with poor sanitation infrastructure. The worm is excreted from an infected host in feces and then enters the ground to wait for a new host.

When a dog or human walks over or touches the infested ground, the worm, which is about half the size of a pencil tip at this stage (0.5 mm), enters the host through the skin to complete a complicated life cycle and establish an infection, which can cause serious illness for the host.

What researchers needed to know about nematodes

“Before we started this, the worms were known to go into the skin head-first. But beyond that, basically nothing was known about the behaviors that they execute to allow them to get into the skin,” said corresponding author Elissa Hallem, a UCLA professor of microbiology, immunology and molecular genetics.

Hallem studies the sensory pathways in the threadworm that help it move through its life cycle and enable it to find and infect hosts. Earlier this year, her lab discovered that the nematodes respond differently to carbon dioxide at different stages in their life cycle, which could help scientists find ways to prevent or cure infections by targeting the CO₂-sensing pathway.

To study behaviors that help the worms penetrate skin, UCLA postdoctoral researcher Ruhi Patel put them on samples of rat skin and human skin and recorded what they did through a microscope. The nematodes had undergone genetic manipulation to make them fluorescent, which was essential for being able to visualize the otherwise translucent worms on the skin surface.

How the nematodes reacted

Patel found that the worms penetrated rat skin very quickly, but they spent up to 10 minutes exploring human skin to find just the right spot before burrowing in. When Patel repeated the experiment with a closely related species of rat-parasitic nematode, she found that it penetrated both human and rat skin but was less effective on human skin, penetrating it only 40% of the time. This suggests that although both types of parasitic worms can penetrate host and non-host skin, they have behaviors specific to host skin that improve their chances of successfully entering it.

“It seems like some parts of the human skin are easier for them to get into than others, and it looks like they’re kind of sampling the skin surface, trying to find a spot where they can get in more easily,” said Patel. “Without these skin-probing behaviors, the parasites are less successful at entering the skin.”

When the researchers edited the S. stercoralis genome to disrupt the gene encoding a specific ion channel called TRP-4, which functions in the neurons that release dopamine, the threadworms almost entirely failed to penetrate the skin. The TRP-4 channel is found not only in threadworms but also in hookworms, another skin-penetrating human-parasitic nematode that is common in parts of the United States. However, the TRP-4 channel is absent in humans.

Based on their findings, the researchers now posit that blocking the function of the TRP-4 channel could be an important mechanism for nematode control. Since humans lack this channel, there would be a very low risk to our own dopamine-sensing pathway. The researchers hope that topical creams or lotions that block TRP-4 or other components of the nematode dopamine-sensing pathway could prevent infections before they even get started.