The BMAA story in a nutshell

Research into the neurodegenerative condition known as Guam ALS-Parkinson Dementia Complex (ALS-PDC) has tended to find itself slightly isolated from the mainstream MND/ALS research world (‘isolated’ being a good word given that the location of the island itself) but I’ve had an interest since I was first introduced to the subject as a PhD student a quarter of a century ago.

This topic was raised once again on day one of the International Symposium on ALS/MND.

Guam map

So where exactly is Guam?

The Guam Story…

For those of you not familiar with this fascinating and convoluted story, the science writer Wendee Holtcamp has written an excellent article on the subject but in a nutshell (an ‘in joke’ for those who know the Guam story) the basis of the hypothesis is that a toxic molecule called BMAA (beta Methylamino-L-alanine) is produced by certain forms of blue-green algae. The theory goes that the residents of Guam for a while were exposed to higher than usual levels through their diet, which led to a high incidence of ALS-PDC on Guam in the 1950s and 1960s.

Taking the theory further, if high levels of BMAA can cause a neurodegenerative syndrome that includes ALS/MND symptoms and pathology, perhaps lower levels of BMAA might act as a subtle predisposing factor for ALS/MND in other parts of the world?

Is there any evidence for this?

The evidence comes from a broad range of sources: there are several epidemiological studies that suggest that the incidence of ALS/MND is higher in areas of coastline and around lakes (where algal blooms will occur) and indeed, BMAA can be measured in the water in those areas.

We also know, from laboratory studies, that BMAA is toxic to neurons – be it cells grown in culture or studies in animals. A pivotal piece of evidence was performed almost 30 years ago, where BMAA rapidly produced severe and wide-ranging neurotoxic effects in lab models. The doses used were particularly high, so there has always been a question as to whether longer exposure to lower doses over longer periods could produce changes more reminiscent of the ALS/MND and dementia seen in humans.

New results were presented on the first day of the Symposium by Dr Paul Cox (Jackson Hole, Wyoming) validating and extending the original research findings. Unfortunately the results are currently under press embargo until the paper is published, but we’ll provide further details when we can. Update: The paper has now been published open-access in Proceedings B.

The small but highly collaborative ALS-PDC research community also held a satellite workshop later that evening. As everyone in the room was familiar with the background story, the program was in the format of a ‘data blast’, with 14 presenters who were given no more than 10 minutes to update everyone on the key points of their latest findings – no waffle, just the facts! Themes covered ranged though epidemiology (from the Arabian gulf, to France, to North America) analytical chemistry (improving ways of measuring BMAA) neuropathology, molecular biology and pharmacology.

The final presentation of the meeting, by Dr Bob Miller (San Francisco) summarised a pilot Phase 1 clinical study of L-serine (an amino acid that can disrupt the action of BMAA) showing that the compound was safe and well tolerated in patients. Dr Miller also highlighted plans for a larger Phase 2 study to be initiated in the USA in 2016. We look forward to hearing more!

Read about the prequel to this latest chapter on the Guam story and blue-green algae in other posts on our research blog: What’s blue-green algae got to do with it? and Guam story discussion at 2011 ALS/MND Symposium.

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