As a Stanford graduate student, University of California, Irvine neuroscientist Dr. John Weiss became fascinated with a story from the distant islands of Guam that involved an unusual paralytic disease. It became the basis of his student research project, which tested the neurotoxicity of the environmental toxin called BMAA, which 30 years later is the basis of research indicating that chronic exposure to BMAA may increase risk of neurodegenerative illness.
The study – published Jan. 20, 2016 in the biological research journal Proceedings of the Royal Society B – was conducted by scientists at the Institute for EthnoMedicine, a nonprofit medical research organization in Jackson Hole, Wyo., and the University of Miami Brain Endowment Bank. The research adds to our understanding of a toxin Weiss first studied in the 1980s.
Brain tangles and amyloid deposits are the hallmarks of both Alzheimer’s disease and an unusual illness suffered by Chamorro villagers on the Pacific Island of Guam, whose diet is contaminated by the environmental toxin BMAA. Pacific Islanders with this unusual condition also suffer from dementia and symptoms similar to Alzheimer’s disease, ALS and Parkinson’s disease.
The cause of neurodegenerative disease remains largely unknown, and the role of environmental factors in these illnesses is poorly understood. However, scientists have suspected a link between BMAA, a neurotoxin found in some harmful algal blooms, derived from cyanobacteria, and also in the brains of people suffering from ALS and Alzheimer’s disease. Once known as blue-green algae, cyanobacteria produce blooms – large floating masses in warm, low water reservoirs and in the world’s oceans.
As a PhD student, Weiss found that adding bicarbonate to the culture medium for neuronal cells significantly increased the toxicity of BMAA. More recently, he and his graduate students at UC Irvine have found that BMAA specifically kills subpopulations of motor neurons, the type that die early on in ALS patients.
Weiss is a professor of neurology and anatomy & neurobiology working to understand Alzheimer’s disease, ALS, stroke and epilepsy.
In the Proceedings study, the EthnoMedicine and Miami scientists conducted two separate experiments on vervets for a period of 140 days. In the first experiment, vervets fed fruit dosed with BMAA developed neurofibrillary tangles and amyloid deposits similar to Pacific Islanders who died from the disease. Vervets fed equal amounts of L-BMAA and the dietary amino acid L-serine had a reduced density of tangles. Vervets fed a placebo dose did not develop neuropathology.
A replication experiment was conducted which added a BMAA dose closer to the amount Chamorro villagers would be exposed to over a lifetime. The first group received fruit containing L-BMAA, the second group received fruit containing one-tenth of the regular dose of L-BMAA, the third group received fruit containing equal amounts of L-BMAA and L-serine, and the fourth group received fruit containing a placebo. After 140 days, tangles and amyloid deposits were found in the brain tissues of all of the vervets who consumed BMAA.
After many years of working on the role of BMAA in Alzheimer’s and ALS, Weiss said, "the demonstration that feeding of BMAA in animal models induces characteristic neurodegenerative disease associated changes in the brain is extremely exciting and important. But more studies will be needed to more fully understanding the ways in which environmental toxins may contribute to human disease, and to test new therapeutic approaches."
"For many years, genetic causes have been the major interest in ALS research, even though gene-environment interactions have long been believed to cause the disease,” he added. “These new results heighten the interest in environment toxins, particularly BMAA, as possible triggers for this serious illness. I am hopeful that this new understanding shows the potential for the exploration of a new generation of ALS drugs."
Tom Vasich / UC Irvine Strategic Communications