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If you have a dog or a cat, you might give them a pill every month to stop them from getting fleas or ticks, which means that you can worry a little less about your pet getting bitten on those hikes or during outdoor playtime, especially since a lot of those parasites can lead to serious illnesses like Lyme disease. But that might get you thinking, "Why can't I take a human version of those anti-tick medications?" Well, this is one of those strange cases where medical advances happened for animals first. And while you definitely should not be dipping into your furry friend's medicine cabinet, you might see something similar hit the pharmacy shelves in the near future.

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The class of flea and tick-killing drugs that we're talking about in this episode are isoxazolines; you might better know them as Nexgard, Bravecto, or Simparica, to name just a few brands. Each of those have a different type of isoxazolines, but they all work pretty much in the same way. These drugs work by turning your dog or cat's blood into poison. For insects, anyway. Once those pests eat your furry friend's blood, the medication blocks certain chloride channels on the insect's nerve cells. Normally, chemical messengers like gaba or glutamate bind those channels and help control how they send signals. But if the medication blocks those channels up, the nerve cell can't send its signals, and the parasites become paralyzed and die.

Now, even though vertebrates like dogs and cats and other mammals also have gaba receptors, isoxazolines don't really bind to them as well as those in invertebrates. Invertebrate's receptors are actually made of different molecular subunits, so they're not quite the same. That's why isoxazolines can poison the biting pests without hurting our pets.

Just to be super clear, these drugs don't stop insects or arachnids from biting; they just kill the blood-suckers pretty soon after they chow down. And because it takes somewhere between 24 and 48 hours for the bacteria that causes Lyme disease to move from the tick into the host, that means these drugs are still effective at stopping the spread of Lyme disease, even though they don't stop bug bites.

So, yeah, there's a good reason why we might want a human version of this drug, too. Right now, Lyme disease is the most common vector-borne disease in North America. Worldwide, around 14% of people have had Lyme disease at some point. And with climate change, tick season lasts longer, and there are more areas where ticks can survive, which all means more ticks and more Lyme disease.

Plus, it's not just the Lyme that we need to worry about; there are lots of tick-bourne illnesses out there, including one called "alpha-gal syndrome" that makes you allergic to red meat. So, it would be great if we had a drug to protect us as well as the usual long pants, and tick checks post hike. And it definitely seems possible.

In 2018, researchers showed that the isoxazolines found in Nexgard and Bravecto could theoretically be repurposed for people, too. Not only that, but these medicines wouldn't just kill ticks; they'd even be effective at killing one of the biggest nuisances of summertime out there - mosquitos. While the medicines would not prevent mosquito bites from happening, turning one of their favorite meals into a poison pill would do a number on mosquito populations, especially in places where mosquitoes spread really serious diseases.

Using computer modeling, the scientists showed that giving just a third of the population these drugs could mean a substantial drop in the number of people who get malaria or Zika. And in 2021, another group of researchers showed that a different isoxazoline, lotilaner, could even kill the lice that infect humans. Both of these studies came out a few years after isoxazolines became available for pets back in 2014.

But almost a decade after they first became available, we still don't have a human version of these drugs. One reason, some people were nervous about the drugs being toxic to mammals. Like we said, while we have different gaba receptors than invertebrates, we still have them, so there's a potential for risk if the medicine binds to our nerves and causes mayhem.

In 2019, vets around the US started getting reports of dogs and cats who had neurological side effects, like seizures or uncontrolled shaking, after taking isoxazolines. They thought this might have to do with some individual animals being more susceptible to the drug getting into their central nervous systems, say because of their genetics, when they last ate, or their age or sex. Although there have been some reports of negative side effects of these drugs, the rate is pretty low, so the FDA still considers them safe medications. But since there haven't been any studies on how toxic these drugs would be in people, we can't just pop the drugs into our medicine cabinets right away.

Another reason we haven't seen a human version just yet is that this is a rare case of pet pharmaceuticals progressing faster than human drug development. While the approval process for drugs for our four-legged friends is fairly similar to ours, the pet pharma industry is much, much smaller. So most of the time, there's more financial push to get a human drug out first and then figure out if it works on other animals later. Despite that, the approval process for veterinary pharmaceuticals is much more streamlined. It doesn't mean there are lower standards; just that it's easier to get ethics approval for testing things on animals than it is on people. Plus, pets have shorter lifespans, so it's quicker to study the lifetime effects of medicines in them than it is for us.

But even now that we've decided that isoxazolines might be a good idea for people, it's still tricky to move a drug over from other animals to humans. For one, developing a drug for human testing takes a lot of time and money. Researchers first need to do those extra toxicology studies I mentioned and figure out exactly what the human dosage and formula is going to be, and understand how our bodies might metabolize the drug. And that is before they even go ahead with any trials.

But despite the hurdles, there is currently an isoxazoline medication in phase two human clinical trials. And the company developing it, Tarsus Pharmaceuticals, says it would help prevent the spread of not just Lyme disease but also malaria by reducing mosquito populations where people are. So, who knows - maybe a few years from now, you will be taking your own anti-tick pill once a month alongside your pet. Just one more thing you two will get to do together.

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