For many years researchers have been looking for the causes of MND but in the majority of cases, a cause and a cure remain elusive. Although now over 20 different genes have been associated with MND, only 8-10% of cases are genetic (also called familial ALS or fALS) versus more than 90% being sporadic (sALS) or of unknown origin. My work focuses on the environmental causes for MND.
“...8-10% of MND cases are genetic versus more than 90% being sporadic or of unknown origin.”
Several years ago, when I was working in heart research, we were approached by ethnobotanist and a TIME magazine, "Hero of Medicine" from the Institute for Ethnomedicine, in Jackson Hole, Wyoming, Dr Paul Cox. Dr Cox was one of the original researchers to identify a link between blue green algae and MND. With his expertise in plants and ours in cells, he reckoned that together we could figure out a puzzle that had been bugging the research community for years – why did a toxin found in blue green algae called BMAA appear to concentrate up the food chain causing neurodegnerative illnesses in animals and humans?
This had first been observed on Guam when blue green algae was identified at the roots of cycad trees, which concentrated in the seeds of the plant and in even higher concentrations in the fruit bats that fed on the seeds (both of which were food sources for the locals).
The terms motor neurone disease (MND), amyotrophic lateral sclerosis (ALS) and Lou Gehrig's Disease are interchangeable. MND is used in Australia, whilst ALS and Lou Gehrig's are used in the USA.
Dr Cox thought the high levels of algal toxin found in the locals foods, might be linked the the higher than normal levels of neurodegenerative disease seen on the island - a condition known as lytico bodig or ALS/PDC.
He had seen our work showing that the drug used to treat Parkinson's Disease called levodopa (or L-DOPA) could be toxic to cells in certain conditions, owing to a unique structural property. L-DOPA is very similar to a compound humans normally use in the building blocks of their proteins, and thus can trick cells into thinking it's the same one. When cells use it by mistake, they can make damaged proteins that can eventually kill cells.
Since BMAA also mimics human amino acids, Dr Cox's idea was that it may build-up in the food chain via the same mechanism and this may explain the mechanism that triggers MND in susceptible people.
Well he was right, and we recently published this work with Dr Cox and his colleague Dr Sandra Banack. But importantly, not only did we identify the mechanism by which BMAA might be causing toxicity, we also identified which human amino acid it might be exchanging with, and this opens the door to develop preventative medicines.
The research model pioneered by Dr Cox is unique in that he has assembled an international team of cross-discipline scientists all focusing on solving the problem of dementia. As a group working outside the silo, we have been able to make breakthrough much faster than traditional research, going from the bench to clinical trials in just over two years.
Now that we have clues to how BMAA might be triggering MND, we want to work out a) how to stop it and b) is it possible to reverse the damage?
This work is ongoing and we were recently awarded an ARC grant towards this project. However government funding cuts meant we only received 70% of the money we need to see this work to its fruition. If you would like to donate, please click the link to Macquarie University Faculty of Medicine and Health Sciences and select "MND, environmental causes".