Link between lethal disease and blue-green algae explored

Closing in on ALS?

By Lindsey Konkel, Staff Writer for Environmental Health News

For 28 years, Bill Gilmore lived in a New Hampshire beach town, where he surfed and kayaked. “I’ve been in water my whole life,” he said. “Before the ocean, it was lakes. I’ve been a water rat since I was four.”

Now Gilmore can no longer swim, fish or surf, let alone button a shirt or lift a fork to his mouth. Earlier this year, he was diagnosed with Amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease.

In New England, medical researchers are now uncovering clues that appear to link some cases of the lethal neurological disease to people’s proximity to lakes and coastal waters.

About five years ago, doctors at a New Hampshire hospital noticed a pattern in their ALS patients – many of them, like Gilmore, lived near water. Since then, researchers at Dartmouth-Hitchcock Medical Center have identified several ALS hot spots in lake and coastal communities in New England, and they suspect that toxic blooms of blue-green algae – which are becoming more common worldwide – may play a role.

Now scientists are investigating whether breathing a neurotoxin produced by the algae may raise the risk of the disease. They have a long way to go, however: While the toxin does seem to kill nerve cells, no research, even in animals, has confirmed the link to ALS. 

No known cause

As with all ALS patients, no one knows what caused Bill Gilmore’s disease. He was a big, strong guy – a carpenter by profession. One morning in 2011, his arms felt weak. “I couldn’t pick up my tools. I thought I had injured myself,” said Gilmore, 59, who lived half his life in Hampton and now lives in Rochester, N.H. 

Three years and many doctors’ appointments later, Gilmore received the news in June that the progressive weakening in his limbs was caused by ALS.

Neither Hampton nor Rochester is considered a hot spot for ALS. Gilmore is one of roughly 5,600 people in the United States diagnosed each year with the disease. The average patient lives two to five years from the time of diagnosis.

There is no cure, and for the majority of patients, no known cause. For 90 to 95 percent of people with ALS, there’s no known genetic mutation. Researchers assume that some unknown interaction between genes and the environment is responsible.

In recent years, some of this research has focused on blue-green algae, also known as cyanobacteria.

“There’s a growing awareness of the importance of gene/environment interactions with neurodegenerative diseases. There is more interest in examining environmental exposures, including exposures to cyanobacteria, as possible risk factors for sporadic ALS,” said Paul Alan Cox, director of the nonprofit Institute of Ethnomedicine in Wyoming, which focuses on treatments for ALS and other neurodegenerative diseases.

Cyanobacteria – some of the oldest organisms on the planet – can occur wherever there is moisture. Blooms are fed largely by nutrients in agricultural and urban runoff.

Some cyanobacteria produce toxic compounds that can sicken people. In August, hundreds of thousands of people in Toledo, Ohio, were left without tap water for days when toxins from an algal bloom in Lake Erie were found in the water supply.

While the cyanobacteria toxin that prompted the Toledo water crisis can cause diarrhea, intestinal pain and liver problems, other toxins produced by the blue-green algae can harm the nervous systems of humans and wildlife.

Scientists have long suspected that a cyanobacteria toxin could play a role in some forms of ALS. After World War II, U.S. military doctors in Guam found that many indigenous Chamorro suffered from a rapidly progressing neurological disease with symptoms similar to both ALS and dementia.

Years later, scientists found the neurotoxin BMAA in the brains of Chamorro people who died from the disease. Cyanobacteria that grow on the roots and seeds of cycad trees produce the toxin.

Cox, a researcher in Guam in the 1990s, hypothesized that BMAA worked its way up the food chain from the cycad seeds to bats to the Chamorro who hunted them. But Cox and his colleagues also found BMAA in the brains of Canadian Alzheimer’s patients who had never dined on Guam’s fruit bats. 

In patients who had died from other causes, they found no traces of it. The source of the BMAA in the Canadians remains unknown.

Some researchers have suggested that fish and shellfish from waters contaminated with cyanobacteria blooms may be one way that people ingest BMAA. In southern France, researchers suspect ALS cases may be linked to consumption of mussels and oysters. Lobsters, collected off the Florida coast near blooms, also have been found with high levels of BMAA.

Scientists around the world are investigating how the neurotoxin gets into the body and whether it contributes to disease.

“We don’t really know what exposure routes are most important,” Cox said.

New England’s ALS hot spots

In New Hampshire, Dartmouth neurologist Elijah Stommel noticed that several ALS patients came from the small town of Enfield in the central part of the state. When he mapped their addresses, he saw that nine of them lived near Lake Mascoma.

Around the lake, the incidence of sporadic ALS – cases for which genetics are not a likely cause – is approximately 10 to 25 times the expected rate for a town of that size.

“We had no idea why there appeared to be a cluster around the lake,” Stommel said.

Based on the link between ALS and the neurotoxin in other parts of the world, Stommel and his colleagues hypothesize that the lake’s cyanobacteria blooms could be a factor.

Across northern New England, the researchers have continued to identify ALS hot spots – a large one in Vermont near Lake Champlain and a smattering of smaller ones among coastal communities in New Hampshire and Maine.

Earlier this year, the researchers reported that poorer lake water quality increased the odds of living in a hot spot. Most strikingly, they discovered that living within 18 miles of a lake with high levels of dissolved nitrogen – a pollutant from fertilizer and sewage that feeds algae and cyanobacteria blooms – raised the odds of belonging to an ALS hot spot by 167 percent.

The findings, they wrote, “support the hypothesis that sporadic ALS can be triggered by environmental lake quality and lake conditions that promote harmful algal blooms and increases in cyanobacteria.”

How people in New England communities could be ingesting the neurotoxin remains largely a mystery. While fish in the lakes do contain it, not everyone in the Dartmouth studies eats fish.

“We’ve sent questionnaires to patients and there’s really no common thread in terms of diet or activities,” Stommel said. “The one common thing that everybody does is breathe.”

In other words, it’s possible that a boat, jet ski or even the wind could stir up tiny particles of cyanobacteria in the air, where people then breathe it in.

Testing the air for a neurotoxin

Last August, at Lake Attitash, Jim Haney, a University of New Hampshire biologist, waded knee-deep into swirling green water. Cyanobacteria were blooming at the small lake in the northeastern corner of Massachusetts. Haney had rigged up three vacuum-like devices with pipes, plastic funnels and paper to suck up and filter air near the lake’s surface.

He took the filter papers back to his laboratory and measured the cyanobacteria cells, BMAA and other toxins stuck to them.

“We want to know what level lake residents may be exposed to through airborne particles,” said Haney, who is sampling the air at Massachusetts and New Hampshire lakes in collaboration with the Dartmouth team.

Stommel said,“it’s very compelling to look at the filter paper and see it just coated with cyanobacteria.”

At this point, Haney and graduate students are trying to understand under what conditions the toxins might be coming out of the lake and whether the airborne particles are an important route of exposure. Preliminary findings suggest that BMAA and other cyanobacteria cells are being aerolized. 

“There is potentially a large quantity of cyanobacteria that could be inhaled,” Haney said. He noted, however, that the measurements were taken about eight inches above the water's surface, making it likely that concentrations would be much lower farther away.

While the toxins are likely to be most abundant in the air around lakes, they exist all over the planet, even in deserts.

In 2009, BMAA was even detected in the sands of Qatar. Crusts containing cyanobacteria may lie dormant in the soil for most of the year, but get kicked up during spring rainstorms. Cox and colleagues hypothesized that breathing in toxins from dust might be a trigger for a doubling of ALS incidence in military personnel after Operation Desert Storm.

Near Haney’s workstation at Lake Attitash, a child splashed in the shallow water off a dock. Haney scooped up a cupful of water. He peered at the tiny green particles in the cup that reflect the sunlight, making the mixture resemble a murky pea soup.

“We’ve developed this view of nature as idyllic, which is wonderful, but not everything in nature is benign,” he said. “Rattlesnakes are natural and you wouldn’t get too close to one of those.”

“Proximity does not equal causality”

The hypothesis that exposure to BMAA may trigger the disease in some people remains controversial.

Researchers have evidence that people living close to lakes with blooms may be at increased risk for ALS. They’ve even found BMAA in the diseased brain tissue of people who have died of neurodegenerative diseases. 

Nevertheless, “proximity does not equal causality,” said Deborah Mash, a neuroscientist at the University of Miami in Florida.

The big, unanswered question is whether the toxin can actually cause the disease. So far, there’s little evidence to show how it could induce the type of brain changes seen in people with ALS.

Tests of human cells have found that BMAA kills the motor neurons – nerve cells that control muscles – implicated in ALS. Primates fed high levels of BMAA in the 1980s showed signs of neurological and muscular weakness. But the toxin did not kill their motor neurons.

“What is lacking at this point is a clear animal model that demonstrates that BMAA exposure results in ALS-like neuropathy,” Cox said.

So what is a possible mechanism for how the toxin may lead to the disease? The body may mistake BMAA for the amino acid L-serine, a naturally occurring component of proteins. When the toxin is mistakenly inserted into proteins, they become “misfolded,” meaning they no longer function properly and can damage cells.

Cox and colleagues soon will test two drugs in FDA-approved clinical trials. They’re about to enter second-phase testing with L-serine. The idea, explained Sandra Banack, a researcher at the Institute for Ethnomedicine, is that large doses of L-serine may be able to “outcompete” low levels of BMAA in the body, preventing it from becoming incorporated into proteins.

For ALS patients like Gilmore, the research can’t come soon enough. “If they can figure out a cause, then hopefully they can find a cure,” Gilmore said.

Follow Lindsey Konkel on Twitter. For questions or feedback about this piece, contact Editor in Chief Marla Cone at mcone@ehn.org.