# PLANT TOXINS AND DEMENTIA IN THE WESTERN PACIFIC

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 1992 · $78,174

## Abstract

Lathyrism, a motorneurone disease of India and Africa, is caused by
beta-oxalylaminoalanine (L-BOAA) which is present in the seeds of the
legume Lathyrus sativus.  The seeds of this plant are ground to a flour
and used as food.  Circumstantial evidence suggests that a second
neurotoxic non-protein amino acid, beta-methylaminoalanine (L-BMAA),
which is present in seeds of Cycas circinalis, which is used as a source
of starchy foods by the Chamorro people of Guam and elsewhere in the
western Pacific, may be responsible for amyotrophic lateral sclerosis-
Parkinsonism dementia (ALS-PDC) among these people.  Both of these non-
protein amino acids induce motor system disorders when fed to macaques
and both are glutamate agonists.  Another glutamate agonist domoic acid,
which was implicated in Canada in a 1987 outbreak of neurologic
disorders by persons who had eaten contaminated mussels, also has
similar ionic functions in almost the same stereochemical orientation as
do glutamic acid, NMDA, kainic acid, L-BOAA and, significantly, the
physiological-stable complex of L-BMAA with carbonate, a common
physiological ion.

In order to provide more comprehensive data on the potential toxicity of
Cycas circinalis from Guam it is proposed to determine the
concentrations of not only free L-BMAA, but also peptide-bound L-BMAA,
L-BMAA  precursors and related glutamate analogues in all organs of the
plant using material from different plant populations.  The structures
of any unusual amino acids or related compounds will be determined, and
isolated compounds will be evaluated for neurotoxicity.  We have already
detected several unknown ninhydrin-positive compounds in the extract of
Cycas circinalis seeds in addition to the known L-BMAA.

It is possible that some forms of Parkinson's and Alzheimer's diseases
and ALS found in the continental United States may involve dietary
factors.  It is therefore also proposed to determine simultaneously
whether any of the major crop species that contribute to the American
diet contain glutamate agonists or antagonists which, if ingested for a
prolonged period, could induce motor systems disorders.

Plant extracts will be analyzed with high voltage electrophoresis, an
automatic amino acid analyzer and GC/MS.  Isolations will be made on
ion-exchange columns.  Neurotoxicity will first be evaluated in cultured
tissues.  Compounds will be selected for animal testing on the basis of
ionic functions, stereochemistry and glutamate agonist activity.

## Key facts

- **NIH application ID:** 3122555
- **Project number:** 1R01AG010637-01
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **SAM.gov UEI:** V6AFQPN18437
- **Principal Investigator:** TOM J MABRY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $78,174
- **Award type:** 1
- **Project period:** 1992-05-01 → 1997-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122555

## Citation

> US National Institutes of Health, RePORTER application 3122555, PLANT TOXINS AND DEMENTIA IN THE WESTERN PACIFIC (1R01AG010637-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122555. Licensed CC0.

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