Mechanism suggested for Guam illness

A research team has invoked protein chemistry to propose a solution to one of the most puzzling parts of Guam’s long-standing neuroscience mystery.

During the 20th century, the prevalence of the neurologic disease called amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC) rose dramatically among the Chamorro people of Guam and then declined, explains Paul Cox of the National Tropical Botanical Gardens, headquartered in Kalaheo, Hawaii (SN: 5/17/03, p. 310: Available to subscribers at http://sciencenews.org/articles/20030517/fob8.asp). The disease even showed up in Chamorro people at a high rate after they’d left Guam.

Several of the proposed explanations focus on BMAA, a neurotoxic amino acid. Earlier work by Cox and his colleagues found that BMAA is produced by cyanobacteria living symbiotically in the roots of cycad plants, and that the toxin, somehow, grows more concentrated as it moves up the food chain—from symbiotic microbes to cycad hosts to cycad-seed-eating bats to bat-eating people (SN: 12/06/03, p. 366: Available to subscribers at Plants, bats magnify neurotoxin in Guam). The bats, one of several species called flying foxes, are now nearing extinction on Guam.

Because BMAA doesn’t bind readily to fat, one of the biggest challenges to the view that the toxin causes ALS/PDC has been to explain how the disease could turn up long after the BMAA exposure had ended. Wouldn’t the neurotoxin either cause immediate damage or just pass from the body?

Now, Cox’s team suggests that proteins capture BMAA and then slowly release it during the natural course of protein turnover in the body. Susan Murch, also of the botanical gardens, and Sandra Banack of California State University in Fullerton analyzed tissue samples from organisms at different steps in the food chain. When they applied acids to break down the proteins, samples of each type of organism released large amounts of BMAA. The results appear in an upcoming Proceedings of the National Academy of Sciences.

“It’s a provocative idea that’s worth following up,” says Peter Spencer of Oregon Health & Science University in Portland. He’s the scientist who first proposed a role for BMAA in the Guam disease.

Spencer, however, also points out an alternative explanation for the lag between toxin exposure and disease: The immediate insult might trigger an irreversible cellular process that only later produces symptoms.