Supplementing Diet with Amino Acid Successfully Staves off Signs of ALS in Pre-Clinical Study
The addition of dietary L-serine, a naturally occurring amino acid necessary for formation of proteins and nerve cells, delayed signs of amyotrophic lateral sclerosis (ALS) in an animal study.
The research also represents a significant advance in animal modeling of ALS, a debilitating neurodegenerative disease, said David A. Davis, Ph.D., lead author and research assistant professor of neurology and associate director of the Brain Endowment Bank at the University of Miami Miller School of Medicine.
The new research protocol using vervets appears more analogous to how ALS develops in humans, Dr. Davis said, compared to historic models using rodents. When he and colleagues gave the vervets a toxin produced by blue-green algae known as β-N-methylamino-L-alanine, or BMAA, they developed pathology that closely resembles how ALS affects the spinal cord in humans.
When a group of these animals were fed L-serine together with BMAA for 140 days, the strategy was protective – the vervets showed significantly reduced signs of protein inclusions in spinal cord neurons and a decrease in pro-inflammatory microglia. The results were published on February 20 in the prestigious Journal of Neuropathology & Experimental Neurology.
“The big message is that dietary exposure to this cyanobacterial toxin triggers ALS-type pathology, and if you include L-serine in the diet, it could slow the progression of these pathological changes,” Dr. Davis said.
“I was surprised at how close the model mirrored ALS in humans,” he added. Beyond looking at changes in the brain, “when we looked at the spinal cord, that was really surprising.” The investigators observed changes specific to ALS seen in patients, including presence of intracellular occlusion such as TDP-43 and other protein aggregates.
Walter G. Bradley, M.D., F.R.C.P., founder of the ALS Clinical and Research Center at the University of Miami Miller School of Medicine, said: “ALS is a progressive neurological disease, also known as Lou Gehrig’s disease, causing progressive limb paralysis and respiratory failure. There is a great unmet need for effective therapies in this disease. After clinical trials of more than 30 potential drugs to treat ALS, we still have only two that slow the disease progression.”
ALS can progress rapidly in some people, leading to death in six months to two years after diagnosis. For this reason, it is difficult to enroll people in clinical trials, a reality that supports development of a corresponding animal model, Dr. Davis said.
In addition, prevention remains essential. “This is a pre-clinical model, which is really the most important type of model, because once people have full-blown disease, it’s hard to reverse or slow its progression,” he said.
The research builds on earlier findings& from Dr. Davis and colleagues in a 2016 study that demonstrated cyanotoxin BMAA can cause changes in the brain that resemble Alzheimer’s disease in humans, including neurofibrillary tangles and amyloid deposits.
Even with the promise of L-serine, the researchers note there is a bigger picture to their new ALS animal model. “Other drugs can also be tested, making this very valuable for clinical affirmation,” Davis said.
The research also has implications for Florida, as BMAA comes from harmful blue-green algae blooms, which have become more common in the summer months in Florida.
According to Larry Brand, Ph.D., professor of marine biology at the Rosenstiel School of Marine and Atmospheric Science at the University of Miami, “We have found that the BMAA from these blooms has biomagnified to high concentrations in South Florida aquatic food chains, thus our seafood.”
“We are very curious about how BMAA affects individuals in South Florida,” Dr. Davis said. “That’s our next step.”
Future research could attempt to answer multiple questions, including: How common is BMAA in local seafood? What are the risks of exposure through exposure to aerosolized cyanotoxins? Is there a specific group of people who are more vulnerable from this exposure to developing diseases like Alzheimer’s and ALS?
The current research would not have been possible, Dr. Davis said, without interdisciplinary collaboration both inside and outside the University of Miami. Another essential factor is the “very unique research environment” in the UM Department of Neurology. For example, the Brain Endowment Bank allows Miller School researchers access to other investigators and to essential research material.
The study was supported by funding from the Josephine P. and John J. Louis Foundation, the William Stamps Farish Fund and Patrick and Heather Henry and the Brain Research Fund, which was funded by a generous donation from Dr. Rita Eisenberg.