Parasitic worms may be causing an often-deadly seizure disorder that has puzzled scientists for years. The seizures affect at least 17 percent of children in parts of Uganda, and make sufferers look like they’re nodding involuntarily. Right now, the disorder is incurable — but today’s findings mean that there could be ways to prevent it, and the study drops clues toward a future cure.
By analyzing the blood and spinal fluid of people living in Uganda and South Sudan, scientists have identified an antibody that’s more common in people with the seizure disorder, called nodding syndrome. This antibody attacks a protein in the human brain that looks remarkably like a protein that’s also in the parasitic worms, suggesting that the nodding syndrome may have to do with a kind of immunological friendly fire.
When certain people are infected with the parasite, they produce an antibody to fight it off — one that can also kill brain cells, the researchers suggested in the journal Science Translational Medicine. Still, the case isn’t closed yet. For one thing, it’s not clear that the antibodies actually cause seizures by attacking brain cells. For another, only half of the patients with nodding syndrome tested positive for this antibody, which means that something else must be causing seizures for the rest.
For years, researchers have suspected that there’s a link between nodding syndrome and a parasitic worm called Onchocerca volvulus. Blood-sucking black flies spit the worm’s larvae into the wound they create when they bite, and the larvae take up residence under the skin. There, the worms can grow to nearly 20 inches long, and they cluster into little clumps that can itch terribly. If the larvae travel into someone’s eyes, they can eventually lead to blindness. The infection is treatable with anti-parasitic
drugs, which can also curb the parasite’s spread. And larvicides can help wipe out the black flies that spread it. But these interventions aren’t always easy to get in remote parts of Africa, where this worm is endemic in 31 countries.
Places with a lot of these infections also tend to have more cases of nodding syndrome. But the strange thing is that these worms don’t seem to get into the human brain — so exactly how they could be causing seizures has been a mystery. A team of scientists led by Avindra Nath at the National Institute of Neurological Diseases and Stroke set out to solve it. They examined the blood and spinal fluid collected from 55 people with nodding syndrome and 55 people without.
The researchers discovered that about half of the blood samples from patients with nodding syndrome contained high levels of a specific antibody the sticks to a protein called leiomodin-1, found in brain cells. By contrast, only about a third of the healthy controls tested positive for it. This protein looks remarkably like a protein in the parasite, too. That’s why the scientists think that when people are infected with the parasite, some of them produce antibodies to fight it off that also inadvertently kill brain cells containing a look-a-like protein.
To put this hypothesis to the test, the researchers dripped the liquid portion of patient blood samples onto neurons growing in a dish — which killed some of them. When the antibodies were removed from the patient blood sample, though, more of the neurons survived — which suggests that the antibodies can indeed harm neurons. Still, it would have been a better experiment if the researchers had tested how the neurons fared when they were treated with patient versus healthy samples.
There are a few other caveats, too — like the fact that leiomodin-1 usually hangs out on the inside of cells, and antibodies can only stick to what they can see on the outside. So it’s not exactly clear how the antibodies can attack something they can’t see. One possibility is that something else, like another branch of the immune system or even the seizures themselves, actually kills the cells, which break open and spill out their contents. That’s when the antibodies come in, and trigger a reaction to leiomodin-1. It’s also possible that neurons flip the protein onto their surface when they’re stressed out.
The authors of an analysis published alongside the study point out that about half of the patients with nodding syndrome don’t actually have leiomodin-1 antibodies — which means that for them, something else is causing their seizures. Nath and his colleagues suggest that there might be other antibodies involved that haven’t been identified yet
What’s more, the research team wasn’t able to say definitively that people generate the leiomodin-1 antibodies in response to the parasite because they weren’t able to sample people before and after they were infected. So, they have more work to do. Still, the authors of the analysis write, with more research, these discoveries could help eventually identify a path to curing nodding sickness. And in the meantime, the study provides even more incentive to wiping out these worms — and the flies that spread them — for good.