BRAIN EXOSOMES FROM BLOOD SAMPLES ALLOW EARLIER DIAGNOSIS OF ALS

Study published in ROYAL SOCIETY OPEN BIOLOGY INDICATES THAT Micro-RNA embedded within small brain particles shed into the blood stream CAN facilitate early diagnosis of ALS  

24 June 2020, Jackson, Wyoming

Exosomes, microscopic packets containing genetic material, are shed by different tissues into the blood. By sequencing microRNA within exosomes originating in the brain, it is now possible to definitively distinguish blood samples of ALS patients from healthy controls, a team of researchers at the Brain Chemistry Labs announced today in Open Biology published by the Royal Society in London. ALS is a progressive neurodegenerative disease that typically affects people in the prime of their life. 

“This discovery is a game changer in ALS research. By sequencing the microRNA within brain exosomes released into the blood, it is possible to rapidly diagnose ALS from a single blood draw. This will allow a much earlier detection of ALS compared to current scientific measures where patients may have to wait for over a year for a confirmed diagnosis,” reports Dr. Sandra Banack, Brain Chemistry Labs Senior Scientist and first author on the new paper. “People with ALS typically live an average of two to three years after diagnosis, so a rapid assessment will allow drug treatment to begin much earlier in the course of the disease.”

The researchers purified brain exosomes from blood plasma by targeting a unique protein on the exosome surface. Using the brain exosomes, the researchers extracted microRNA, short sequences of genetic material that typically regulate gene expression within the cell. Eight different microRNA sequences together form a unique genetic fingerprint that distinguishes blood samples of ALS patients from healthy controls.

According to Dr. Rachael Dunlop, Brain Chemistry Labs Senior Research Fellow, “This new genetic fingerprint may open up opportunities for novel drug discovery. Given the lack of treatments for ALS, physicians and researchers understand the importance of having a new biomarker to help in assessing the effectiveness of new drug candidates, and in enabling patients to receive experimental treatments at an earlier stage of the disease.”  

Dr. Walter Bradley, Chairman Emeritus of the Department of Neurology at the University of Miami Miller School of Medicine, who was not an author on this study, welcomed this advance. “Early diagnosis is the holy grail for many neurological diseases,” he said. “These new results are extremely promising for patients and their physicians.”

Translating these new techniques from the laboratory bench to the clinic may still take time, cautions Brain Chemistry Labs Director Dr. Paul Alan Cox. “We are excited by this discovery,” Cox explains, “but scaling up this new diagnostic method to a high-throughput assay available in the clinic will likely require the resources of a pharmaceutical partner.”

The article, “An miRNA fingerprint using neural-enriched extracellular vesicles from blood plasma: towards a biomarker for amyotrophic lateral sclerosis/motor neuron disease” may be seen online at Royal Society Open Biology (DOI 10.1098/rsob.200116):

https://royalsocietypublishing.org/doi/10.1098/rsob.200116

New Study Indicates Amino Acid May
Be Useful in Treating ALS

Study published in Journal of Neuropathology & Experimental Neurology provides new model for ALS and its treatment 

20 February 2020, Jackson, Wyoming

A naturally occurring amino acid is gaining increased attention from scientists as a possible treatment for ALS following a new study published today in the Journal of Neuropathology & Experimental Neurology. The study showed that the amino acid, L-serine, successfully reduced ALS-like changes in an animal model of ALS. 

The scientists conducted the vervet study at the Behavioural Science Foundation, a specialized research facility on the Caribbean island of St. Kitts. After being exposed to a cyanobacterial neurotoxin called BMAA, the vervets developed aggregations of misfolded proteins similar to those seen in human ALS patients, and activated microglia, a type of immune cells, in their spinal cord and brain, similar to those that occur in the early stages of ALS. In contrast, vervets that also received the amino acid L-serine had significantly reduced ALS pathology.

Dr. David Davis at the Department of Neurology, University of Miami Miller School of Medicine who served as first author on the paper, said that the differences were profound. “Without L-serine co-administration, the BMAA-exposed vervets developed motor neuron degeneration, pro-inflammatory microglia and dense inclusions of TDP-43 and other misfolded proteins known to be associated with ALS,” Dr. Davis explained. “In animals dosed with L-serine, the progression of these ALS-like changes was considerably reduced.”

ALS is a devastating disease that hits people in the prime of life, causing increasing paralysis and often results in death within two to three years after diagnosis. At present, only two drugs are available that slow the disease modestly. This study offers the possibility that L-serine may slow the progression of the disease even more.

Potential Implications for L-Serine as a Treatment

Neurobiologist Dr. Deborah Mash of Nova Southeastern University, who was also an author on the study, said that the results “holds promise for identifying a cause of sporadic ALS, which accounts for 90 percent of all ALS cases.” 

Dr. Elijah Stommel, a Professor of Neurology at Dartmouth Medical School, who was not associated with the study, said that these experimental results are encouraging. Stommel is conducting a Phase II trial of L-serine in 50 ALS patients. “We are attempting to replicate a previous positive trial of L-serine for ALS patients, but won’t know the results until the trial is finished,” he said. 

L-serine is one of the twenty amino acids that make up human proteins. L-serine molecules in proteins are often the site where proteins are phosphorylated, or charged, so they can be properly folded. “Think of a charging port for an electric car,” explained Dr. Paul Alan Cox, Executive Director of the Brain Chemistry Labs in Jackson Hole, “If the cable can’t be connected there, the car can’t be charged.” Scientists at the Brain Chemistry Labs have also discovered that L-serine modulates the unfolded protein response which helps protect neurons from the damage produced by misfolded proteins.

“While these data provide valuable insights, we do not yet know if L-serine will improve outcomes for human patients with ALS,” cautioned internationally renowned ALS expert, Dr. Walter Bradley, who was also an author on the study. “We need to carefully continue FDA-approved clinical trials before we can recommend that L-serine be added to the neurologists’ toolbox for the treatment of ALS. However, this vervet BMAA model will be an important new tool in the quest for new drugs to treat ALS.”

Dr. Larry Brand, a prominent oceanographer unassociated with the study, said that there are even broader implications of the study for human health. “These vervets were exposed to the same cyanobacterial toxin that was found in the brains of beached dolphins with Alzheimer’s neuropathology,” he said. “This is one more indication that we need to carefully monitor the health effects of exposure to cyanobacterial blooms.”

To access the article in Journal of Neuropathology & Experimental Neurology, go to:

https://academic.oup.com/jnen/advance-article/doi/10.1093/jnen/nlaa002/5740037?searchresult=1

Jackson Hole Lab Approach to Alzheimer's Highlighted in Fortune Magazine

18 January 2019, Jackson, Wyoming

A cover story with an accompanying video entitled “Outsmarting Alzheimer’s: How a Small Lab in Wyoming is Changing the Face of Medicine” was posted today on Fortune magazine’s website: http://fortune.com/longform/alzheimers-disease-cure-breakthrough/

Rick Tetzeli’s article compares the unsuccessful approach of the billions expended by big pharma to the more modest ($2.5 million annually) but highly successful approach of Wyoming’s not-for-profit Brain Chemistry Labs. 

Led by Harvard-trained ethnobotanist Dr. Paul Alan Cox, research by five lab scientists and a 50-scientist international consortium, has highlighted the potential of the dietary amino acid L-serine as a means of slowing protein misfolding characteristic of Alzheimer's, ALS, and other progressive neurodegenerative diseases.

“How extraordinarily unlikely and yet wonderful would it be if Cox and his colleagues were right—and the best prevention for some of these terrifying diseases turns out to be a naturally occurring protein building block rather than a high-priced drug?” Fortune opines.

 Pharmaceutical firms have focused on the amyloid hypothesis, the idea that fragments of the amyloid protein in the brain cause Alzheimer's disease. A smaller group of scientists believe that tangles of the protein tau instead trigger Alzheimer's.

 The Wyoming scientists argue that amyloid and tau are symptoms rather than causes of the disease and instead seek cures in the mechanisms of protein misfolding.

The Fortunearticle highlights ethnobotanical research in island villages where Alzheimer's and ALS are frequent versus villages where these diseases are unknown. 

 UCLA Professor of Neurology Dale Bredesen is quoted by Fortuneas saying that “Paul’s work is exciting,” while University of Arizona Professor of Medicine Andrew Weil told Fortune“Cox’s work doesn’t feel so far off the mainstream now.”

 Although L-serine is now the topic of two FDA-approved Phase II clinical trials at Dartmouth, “the jury is still out,” Cox admits, “but we will know a lot more in the year ahead.” 

Contact: Marilyn Asay, 801-375-6214, marilyn@ethnomedicine.org

Brain Chemistry Labs focus on Florida blooms.

August 15, 2018, Jackson, Wyoming

Massive cyanobacterial blooms associated with the emergency release of nutrient-laden Lake Okeechobee water down the St. Lucie river in the summer of 2016 exposed Florida residents to a potent toxin called microcystin which is known to cause liver cancer.

"It is a reasonable prediction that the cohort of Florida State citizens exposed to the 2016 Florida cyanobacteria bloom incident .  .  .  may experience an increased lifetime risk of liver cancer and/or hepatic dysfunction requiring hospitalization or trans-plantation," cyanobacterial expert Dr. James Metcalf and his colleagues report in a paper published today in the British journal Water Policy. 

The malodorous 2016 cyanobacterial blooms, referred to as "guacamole" by some residents, were associated with fish kills and the deaths of 11 manatees in the St. Lucie River and Stuart area, but insufficient warning was provided to citizens about potential human health impacts the paper claims. 

"Neither the State of Florida, nor the U.S. government, currently has water quality criteria or alert levels for cyanotoxins, such as microcystin," Dr. Metcalf and his colleagues find.

"We collected cyanobacterial samples from the area as part of our ongoing research into possible links between neurodegenerative illness and cyanobacterial toxins and were relieved to find only very low amounts of the neurotoxin we are studying ," Dr. Paul Alan Cox, Executive Director of the Brain Chemistry Labs said. "However, when we analyzed the samples in our laboratory for microcystin, we were stunned to find that the concentrations of microcystin were 10,000 times greater than that allowed by the state of Ohio for recreational waters."

Cyanobacterial blooms associated with Lake Okeechobee are a recurring problem in Florida. Metcalf and other researchers from the Brain Chemistry Labs, a not-for-profit research center in Jackson Hole, Wyoming, are once again collecting samples from the current cyanobacterial blooms on the east and west coasts of Florida.

Contacts: Dr. James Metcalf, telephone: 307 734 1680, james@ethnomedicine.org
Marilyn Asay, telephone: 801 375 6214, marilyn@ethnomedicine.org.