What’s blue green algae got to do with it?

Dr Rachael A Dunlop, based at the University of Technology Sydney is interested in sporadic MND and the links to a toxin found in blue green algae. Here she writes about her research:

Back in 1963, researchers descended into the jungles of the South Pacific island of Guam looking for the causes of a strange neurodegenerative disease that manifested as a combination of Parkinson’s, Alzheimer’s and MND. The condition, known locally as lytico bodig, manifested as weakness, wasting, and then paralysis of the arms and legs resulting in patients becoming bed-bound, with difficulty breathing, speaking or swallowing. It occurred at 50-100 times the levels of MND seen in the general population and had decimated the local people. A search for a genetic connection quickly turned up nothing so the researchers went in search of an environmental trigger.

A new toxic amino acid? 

Clues to a cause came from a paralytic disease contracted following the consumption of grass pea from the species Lathyrus sativus, known as neurolathyrism. This permanent paralytic condition has been attributed to an unusual amino acid only found in plants and not normally used by humans to make their proteins – called BOAA or ODAP. Since the Guamanians also suffered paralysis, researchers examined their diet to see if they were also consuming this toxic amino acid.

They didn’t find ODAP but instead identified a new non-protein amino acid (simply meaning not used by humans) called BMAA. Further analysis determined that BMAA was derived from cyanobacteria (more commonly – but incorrectly – known as blue green algae) . But how did a toxin usually found in algae get into the flour used by the local people?

Some clever detective work revealed that around the roots of the cycad trees grew BMAA-synthesising cyanobacteria, and the toxic BMAA was able to bioconcentrate up through the plant and into the seeds. When the locals ground the seeds for flour to make tortillas, they were getting a massive dose of BMAA.

Further confirmation for this bioconcentration came in the form of flying foxes which fed on the cycad seeds. Flying foxes were considered  a delicacy by the local people who consumed them whole in a coconut soup. Analysis of their fur and skin revealed they had very high levels of  BMAA, thus the local people were getting BMAA from the flour as well as the flying foxes.

Exposure to BMAA and blue green algae increases MND risk 

Since then, researchers have observed that people who are exposed to high levels of blue green algae have higher levels of MND. Although there are genes linked to MND, in about 90% of cases the disease just comes on for no known reason. But exactly how could a little molecule like BMAA cause such a devastating disease?

The importance of cross-discipline research 

As cell biologists with decades of experience examining the toxicity of non-protein amino acids, were were alerted to the link between MND and BMAA by ethnobotanist from the Institute for Ethnomedicine,  Dr Paul Cox, who was one of the original researchers to identify the MND link. Dr Cox and colleagues had already obtained evidence showing that people who consume foods contaminated with BMAA have higher levels of MND, and that soldiers who where deployed during the Gulf War of 1991 have more MND (this has recently been attributed to the finding that the desert crusts of Qatar are rich in BMAA producing blue green algae).

Other scientists have also reported that the algal toxin BMAA “builds up” in the food chain, concentrating from the ground to the seeds of cycad trees to fruit bats that feed on the seeds, then to humans who eat the bats. Colleagues from Sweden have also reported the same phenomenon in aquatic species with high levels of BMAA reported in shark fin, lobsters, mussels and crabs. Colleagues from North America have reported BMAA in the brains of patients who died from MND and also Alzheimer’s Disease, making this a potentially large public health problem.

BMAA makes toxic proteins 

As for our contribution, we recently published a paper showing how BMAA might trigger MND in human cells. Consistent with our previous work on DOPA –  a drug used in Parkinson’s Disease which also mimics a human amino acid – we propose that BMAA might be tricking human cells into thinking it’s one of “our own” and accidentally making it into proteins. This might result in the synthesis of proteins that don’t fold properly, these build up to toxic levels and eventually the cells undergo suicide. This might be a trigger for people who have been exposed to BMAA and also have some other susceptibility, possibly genetic in nature, for MND.

Non-protein amino acids cause human and animal disease

Non-protein amino acids causing disease in animals and humans is not new, in fact ODAP was recently implicated in the death of American hiker Chris McCandless (aka Alexander Supertramp) in the Alaskan wilderness in 1994.

McCandless’ emaciated body was found by moose hunters in a bus he was sheltering in, only 4 months after he ventured into the wilderness. For many years it was assumed he starved to death as a result of lack of food and isolation but only recently a new hypothesis was proposed after fresh evidence came to light.

Right before Chris died he had taken a self portrait holding a note pleading for help since he was “extremely weak, fault of potato seed, much trouble just to stand up, starving, great jeopardy”. When the seeds were analysed it was determine they were rich in ODAP, thus, it seems likely he did die of starvation but as a result of a type of neurolathyrism contracted from consuming contaminated seeds.

Non-protein amino acids have also been linked to Birdsville Disease in horses, Zamia staggers in cattle and lupus in humans.

What does it all mean? 

Because we think we know how BMAA might be triggering disease, it also means we might be able to stop it and this opens up the door for the design of therapies.

We wrote about Rachael’s research in 2013. You can read about it here.