References

146 S.J. Murch
On Guam and in other Pacific locales, indigenous residents and immigrants
have experienced an epidemic of progressive neurodegenerative diseases
that manifests as atypical parkinsonism, dementia, motor neuron disease,
or a combination of these three phenotypes. The Chamorros of Guam
call the disease lytico-bodig, while neuroscientists refer to it as the amyotrophic
lateral sclerosis/parkinsonism-dementia complex (ALS/PDC). In
the 1950s, at the height of the epidemic, ALS/PDC was 100 times more
prevalent than ALS elsewhere in the world (Kurland and Mulder 1954; Mulder
et al. 1954). The disease of Chamorros is clinically and pathologically
like classical ALS, with additional similarities to Alzheimer’s disease, and
Parkinson’s disease. It has often been called the “Rosetta Stone” of neurological
disease as it is thought that understanding ALS/PDC on Guam may
provide the keys to understanding progressive neurodegenerative diseases
elsewhere. The exact cause of the disease remains uncertain but epidemiological
research on Guam has implicated environmental factors rather
than genetic predisposition, infectious agents or mineral imbalances. At
the climax of the epidemic ALS/PDC was the main cause of death of adult
Chamorros but the incidence of the disease has steadily declined in recent
decades, potentially as a result of western influences on Chamorro culture.
Today the disease occurs only in older people, and rarely in any individual
born after 1960. The study of this older generation of Chamorros and
the Chamorro culture is essential to understanding of the disease and the
search for disease causes.
In 1967, Kurland and Whiting began ethnobotanical studies to determine
if the Chamorro culture, lifestyle and diet might be implicated as the cause
of ALS/PDC. Flour made from the seeds of the indigenous cycad (Cycas
micronesica Hill.) was extensively investigated. The Chamorros knew the
cycad seeds to be acutely toxic and detoxified the flour made from seeds
by multiple washings over a 3-week period. Chemical examination of the
cycad flour and cycad seeds led to the discovery of the unusual non-protein
amino acid BMAA (Vega and Bell 1969). BMAA is distributed across all
tissues in cycad plants but is most concentrated in the reproductive tissues
where it potentially protects gametes from herbivory and has ensured the
survival of the species over three hundred million years (Banack and Cox
2003a). Interestingly, new information indicates that the neurotoxin BMAA
mayalsoplayaroleinplantphysiology.ArecentstudywithArabidopsis
seedlings demonstrated a 2–3-fold increase in hypocotyls elongation and
inhibition of cotyledon opening when seeds were germinated in the presence
of low concentrations of BMAA (Brenner et al. 2000).
In animal systems, BMAA has an established toxicity of about 0.4 mg/g
(Polsky et al. 1972). Spencer et al. (1986) suggested that BMAA might be
a cause of ALS/PDC and fed monkeys with large doses of BMAA, causing
acute damage to motor neurons in the spinal cord producing a flaccid