Hanover
The answer may help scientists, including researchers at Dartmouth-Hitchcock, develop a better understanding of the environmental causes of illnesses such as Lou Gehrig’s disease (amyotrophic lateral sclerosis, or ALS), Alzheimer’s disease and Parkinson’s disease and find ways to prevent and treat them.
That research is the subject of Toxic Puzzle: The Hunt for a Hidden Killer, a documentary produced by Utah-based Scandinature Films USA and narrated by Harrison Ford that will be screened at the Hopkins Center in Hanover on Tuesday.
“It’s an important story to tell,” said filmmaker Bo Landin in a phone interview from Heber City, Utah.
While most people who are exposed to cyanobacteria — blue-green algae that can produce the neurotoxin beta-Methylamino-L-alanine, or BMAA — will not develop a neurodegenerative disease, Landin said, it’s important for people to have as much information as possible so they can make informed decisions about their exposures.
Neurodegenerative illnesses — characterized by amyloid protein clumps and tangles of neural fibers in the brain, which can cause problems such as dementia and/or progressive muscle weakness — come in several different forms, likely resulting from different environmental or genetic causes, said Dr. Elijah Stommel, a D-H neurologist.
These illnesses do not have cures, but in some cases there are treatments that slow their progress. Stommel said research, including his own, connecting cyanobacteria to these diseases shows promise both for treatment and prevention.
There’s “still a lot of work to be done, but it’s hopeful,” said Stommel, who is interviewed in the film about his research relating to ALS and cyanobacterial blooms in New Hampshire, particularly in Mascoma Lake.
Landin’s interest in the subject stemmed from a conversation over dinner with Paul Cox, a Wyoming-based ethnobotanist whose study of BMAA has helped bring together scientists from different disciplines and areas of the world.
Following that conversation several years ago, Landin, who is also a trained biologist, began documenting this area of research, before some of the key findings had been published.
This is Landin’s second film about Cox and his work. The first was Nafanua and the Triangle of Life. Completed in 1991, that film described Cox’s work in Samoa to find prostratin, a plant-derived drug used to treat HIV and his related work to protect the rainforest where he found the medicine-producing plant.
Toxic Puzzle, which premiered last month at the Newport Beach Film Festival in California, draws connections between research in different fields and parts of the world. The film includes Cox’s work in Guam, where he and other researchers made a connection between the Chamorro people’s diet and dementia and paralysis that they developed after World War II.
Previous studies had shown that cycad seeds, which the Chamorro made into flour, contained BMAA, but not in sufficient quantities to cause illness.
In a paper published in 2003, Cox showed that another common food in the Chamorro diet — flying foxes, which also eat cycad seeds — contained BMAA in larger quantities, sufficient to cause illness.
In the film, Landin connects the work in Guam to other scientists’ work in Sweden where they found BMAA in fish from the Baltic Sea, which commonly has large numbers of cyanobacterial blooms. Landin also traveled to Japan with Cox, who found that residents of Ogimi village on the island of Okinawa who were living into their 100s and 110s without memory or muscular problems consumed high quantities of the nutrient L-serine, found in foods such as soy products and seaweed. The villagers ate more than 8 grams of the nutrient per day, compared to less than 3 grams per day an average American consumes, according to Cox’s study.
Landin also brings in work that Australian researchers have published, which found that L-serine can help ward off damage to the brain caused by BMAA. The film also describes work published last year demonstrating that exposure to BMAA can cause neurodegeneration in vervet monkeys and that increasing L-serine intake can help slow the disease.
In the film, Stommel describes his work to find 11 clusters of patients diagnosed with ALS around lakes in northern New England. While the disease is still relatively rare — about five per 100,000 people in the U.S. have ALS, according to the Centers for Disease Control and Prevention — researchers found that people were 10 to 25 times more likely to develop ALS when they lived around Mascoma Lake.
Exposure to cyanobacteria may be one of several risk factors contributing to ALS, said Stommel, who specializes in the treatment of ALS. Other risk factors may include athleticism, head trauma, and exposure to heavy metals, pesticides and solvents, Stommel said.
Risk for developing ALS, however, is just one of many reasons to avoid cyanobacterial blooms, Stommel said. Cyanobacteria can cause liver disease, kill animals and affect tourism, he said.
Dartmouth-Hitchcock neurologist Aleksandra Stark aims to find another piece of this puzzle through a phase II drug trial of L-serine, the nutrient that has shown the ability to slow the development of Alzheimer’s disease in vervet monkeys.
The trial, a collaboration with Cox’s Institute for Ethnomedicine, aims to determine the safety of consuming 15 candy-like “gummies” containing one gram of L-serine each, twice daily.
Researchers aim to enroll 40 patients with early-stage Alzheimer’s disease. Such patients have “mild dementia,” said Stark, meaning that they are still mostly independent though they sometimes may require help.
In the double-blind trial, which began enrolling patients in March, neither patients nor researchers know which patients get L-serine and which get gummies without L-serine.
So far, the trial has four people enrolled and researchers will be enrolling more people over the course of the next year and a half, Stark said. She is enrolling patients of her own and welcomes referrals from other providers, she said.
Based on previous studies, she expects to find that L-serine has few side effects, aside from minor bloating and gas, she said.
Though this phase II trial is simply aimed at evaluating L-serine’s safety, Stark hopes that future studies will show L-serine slows cognitive decline or even reduces cognitive impairment, she said.
“I’m really hopeful that it’s going to work,” Stark said. “The preliminary data was positive and really exciting.”
Cox plans to pursue a similar trial for ALS patients, but is still fundraising for it. He expects to begin enrolling patients by the end of the year, he said.
In the meantime, Stommel recommends that his ALS patients try taking L-serine as a supplement.
“No harm done,” he said. (After developing symptoms, ALS patients typically live two to five years.)
Though some patients may experience some gastrointestinal discomfort, “If it actually were to help, it sure beats getting a worsening ALS,” he said.
He has yet to see any of his patients completely stabilize while taking L-serine, Stommel said. Should researchers find a “cure” for ALS, Stommel said he imagines it will be a “cocktail of different things.” Similarly, Stark said she expects an Alzheimer’s cure would also be multipronged.
Through the film, Landin said he aims to translate a large collection of research into language that everyone can understand.
“In this case, what they are doing at Dartmouth is so amazing,” he said. “I think more people in and around Dartmouth should know that. It touches — definitely — the daily lives of people living there.”
Editor’s note: Two screenings of Toxic Puzzle, which runs 1 hour and 23 minutes, are scheduled to be shown on Tuesday, at 5 and 7:30 p.m., at the Hopkins Center for the Arts’ Loew Auditorium. Stommel, Cox and Landin will be present for a question-and-answer session after each screening. Tickets are $5. More information about the film is available online at hop.dartmouth.edu/online/toxic-puzzle. Staff writer Nora Doyle-Burr can be reached at ndoyleburr@vnews.com or 603-727-3213.
