A story from the deserts of the Middle East during the first Gulf War could potentially end with a cure for Alzheimer’s disease.
Dr Aspa Chatziefthimiou, a microbial ecologist and research scientist at Weill Cornell Medicine – Qatar (WCM-Q) is part of an international consortium of more than 50 scientists researching neurodegenerative diseases like Alzheimer’s, Parkinson’s and ALS. She is examining the role of desert cyanobacteria – previously called blue-green algae – and how the neurotoxins they produce may be at least partly responsible for the onset of a variety of neurodegenerative diseases.
The possibility that desert toxins may have a role was first noticed in the decade following the first Gulf War and the liberation of Kuwait. Dr Chatziefthimiou explained:
It was found that the US military personnel who were deployed in the first Gulf War had three times the incidence of ALS compared to their colleagues with the same training but who were not deployed to the Gulf. These soldiers trained together in the US and had similar backgrounds and experiences. The hypothesis was that what caused the subsequent disease was the inhalation of dust particles in the desert. These personnel were following military vehicles in the desert which were physically disturbing biocrusts containing cyanobacteria and the toxins they produce and aerosolising them.’
The interest in cyanobacteria as a potential cause of neuro-degenerative disease was originally sparked by ethnobotanist Dr Paul Cox, the executive director of Brain Chemistry Labs, a not-for-profit research centre based in Wyoming.
Dr Cox and his colleague Dr Sandra Banack discovered that local villagers on the Pacific island of Guam had a high rate of neurodegenerative disorders because of their predilection for eating native fruit bats. The bats were eating the seeds of the cycad tree and a toxin in the seeds called BMAA (beta-N-methylamino-L-alanine), was accumulating in the tissues of the bat. The toxin itself was produced by cyanobacteria found in the roots of the cycad trees.
BMAA damages neurons in a number of ways and so is thought to cause brain disorders like Alzheimer’s. While searching for ways to block the neurotoxin, Dr Cox and colleagues found that the commonly occurring amino acid L-serine not only blocked BMAA but was also neuroprotective. They are now investigating, through FDA-approved human clinical trials, whether L-serine could prove to be a therapy for neurodegenerative diseases like Alzheimer’s. Dr Chatziefthimiou said:
We now know that BMAA is one causative factor for neurodegenerative diseases, it’s one of multiple stressors. We have found that L-serine offers neuroprotection and we believe that it can slow down the progression of the disease.’
She said that a 2016 study involving primates conducted by Dr Cox and his team had potentially positive results; one group of monkeys were fed food with BMAA present, another food with L-serine and a third with both BMAA and L-serine present. A control group received unadulterated food.
The researchers found that the monkeys fed BMAA developed brain tangles and plaques associated with Alzheimer’s, while those fed BMAA and L-serine combined had an 80% lower density of brain tangles. More recently, a phase I clinical trial showed that L-serine is safe for human consumption and that ALS disease progression was slowed by 85% (ALSFRS-R scale) at the highest dose tested. The current ALS phase Iia clinical trial at Dartmouth-Hitchcock Medical Centre in New Hampshire is seeking to replicate these results.
L-serine is a readily available and inexpensive food supplement and found naturally in food such as sweet potatoes, turkey and tofu among others.
Dr Chatziefthimiou, in collaboration with the Brain Chemistry Labs and Dr Renee Richer, a former associate professor of biology at WCM-Q, is examining how the cyanobacteria and their toxins that are found in Qatar in both the desert and the marine environment are transmitted to humans through the marine food chain, drinking water and the air, although she stressed that there is no cause for alarm and that cyanobacteria are regularly found in almost every environment on Earth. In deserts particularly, cyanobacterial crusts are vital as they keep the soil fertile and set the stage for vegetation to take root. Dr Chatziefthimiou said:
We find cyanobacteria and their toxins in all tested samples of seawater, cyanobacterial crusts and marine mats. When we tested for BMAA in water tanks and the marine food chain in Qatar – including crabs, snails, shrimp and fish – all the samples were free of BMAA. Other associated toxins which can transform into BMAA were present, but did not biomagnify up the food chain i.e. the larger organisms don’t contain greater levels of the toxins when compared to the base of the food chain. This was a surprising finding, contrasting work by colleagues that clearly show that BMAA is present and biomagnifies in marine food chains in Florida, US or in the Baltic Sea, Sweden.
Our conclusion is that the way the toxins behave are climate- or regionally-dependent, and so the scientific queries used to inform policy and regulations for the protection from exposure to these toxins, should be regionally based as well. These research findings have been published in the journals ‘Neurotoxicity Research and Toxicon’. We think the cyanobacteria may produce the BMAA toxin as a means of communication, so it would be the equivalent of a text message in humans or a distress call in birds. They may communicate with the toxins when the environmental conditions change or when nutrient levels change. We also see that these toxins are persistent or have long residence times in the environment, even when they are not actively being produced.
Now we are looking at further evidence of how and why the toxins are produced. How are they transformed from one to the other? What is their half-life in the environment? How are they transported with sand storms and how do they affect our outdoor air quality? These are questions we try to answer from an ecological standpoint.’
Dr Chatziefthimiou’s research is supported by a National Research Priorities Project grant: 4-775-1-116: ‘Toxin Production by Desert Cyanobacteria’ from the Qatar National Research Fund, which was awarded to Dr Renee Richer, who is currently an assistant professor at the University of Wisconsin in the US.