Violet Research in Wyoming May Lead to Glioblastoma Cure.

Research on violets in Jackson Hole may lead to a powerful new treatment for glioblastoma.

Glioblastoma is an extremely dangerous form of brain cancer affecting both children and adults, with most patients perishing within nine to twelve months from diagnosis.

Surgery to remove the tumors is particularly difficult in children.

The FDA-approved chemotherapy TMZ is effective in only 50 per cent of cases, with rapid development of resistance to TMZ among the cancer cells.

Violet researcher Dr. Samantha Gerlach at Brain Chemistry Labs. Photo courtesy of Dr. Paul Alan Cox, Brain Chemistry Labs.

The Brain Chemistry Labs in Jackson has taken an innovative approach to glioblastoma treatment based on cyclotides—small circular peptides—extracted from violets.

Scientists there have demonstrated that in the test tube cyclotides can increase the power of TMZ to kill glioblastoma cells eight-fold.

Cyclotides, however, are found only in minuscule concentrations in violets. Brain Chemistry Labs researchers have found a way to produce in sufficient quantity synthetic versions of cyclotides from violets for further testing in mice.

A generous grant from the Dr. Denis R Lyman & Diane Kay Robards Lyman Foundation in Wyoming will enable cutting-edge research by the Brain Chemistry Labs in Jackson to develop and test a novel new glioblastoma treatment option.

Caption: Wyoming violets. Photo courtesy of Dr. Paul Alan Cox, Brain Chemistry Labs

This gift will enable Brain Chemistry Labs research fellow and New Orleans Dillard University Professor Dr. Samantha Gerlach to continue her studies on how to produce sufficient synthetic violet molecules to conduct human clinical trials.

Together with collaborator Dr. Christian Gruber of the Medical University of Vienna, the safety and effectiveness of the synthetic violet molecules will be determined as a step toward moving to human clinical trials.

The intended outcome is for mass-produced synthetic violet cyclotides to serve as a powerful tool to combine with current TMZ therapy to turbocharge glioblastoma treatment without creating resistance from the glioblastoma cells.

Neurotoxin BMAA found in dust from Great Salt Lake.

In a startling discovery, researchers have identified a chronic neurotoxin known as BMAA in dust particles from the Great Salt Lake's dried lakebed. This toxin, linked to neurodegenerative illnesses, has become a significant health concern due to its presence in windblown dust that reaches populous metropolitan areas along the Wasatch Front.

Dr James Metcalf collects dust samples from the Great Salt Lake.

The dust, enriched with heavy metals and now with identified cyanobacteria and their toxins, poses an unsettling environmental health risk.

Studies have indicated that chronic dietary exposure to BMAA can trigger ALS-type neuropathology, with the neurotoxin now considered the most substantial environmental risk factor for developing Amyotrophic Lateral Sclerosis (ALS).

Although BMAA exposure also causes laboratory animals to form Alzheimer’s-type neuropathology, its role in Alzheimer’s, as well as Parkinson’s, is not fully understood.

However, its connection to ALS has been corroborated by two recent epidemiological studies, marking it as the most robust environmental link to the disease thus far.

Notably, Dartmouth researchers observed a higher risk of ALS in residents living near cyanobacteria-infested rivers and lakes in New Hampshire, underscoring the potential hazard of BMAA exposure.

Studies have indicated that chronic dietary exposure to BMAA can trigger ALS-type neuropathology, with the neurotoxin now considered the most substantial environmental risk factor for developing Amyotrophic Lateral Sclerosis (ALS).

Furthering the concern, the nonprofit Brain Chemistry Labs in Jackson Hole has been monitoring BMAA and other cyanotoxins in water bodies like Lake Okeechobee and collaborating with the Calusa Water Keeper to study airborne cyanobacterial toxins in Florida.

International research groups from Sweden, China, and France are also investigating chronic BMAA exposure as an ALS risk factor.

While ninety percent of ALS cases are sporadic and ten percent familial, the threat posed by the inhalation of BMAA-laced dust remains unclear.

What is clear, however, is the urgent need for comprehensive studies to determine the potential increase in ALS risk due to exposure to the Great Salt Lake dust.

The study was published this week in the journal Toxins.

Cyanotoxin Analysis of Air Samples from the Great Salt Lake. James S. Metcalf, Sandra Anne Banack and Paul Alan Cox. Toxins 2023, 15(11), 659; https://doi.org/10.3390/toxins15110659


Wyoming Non-Profit Brain Chemistry Labs Hosts Global Symposium on Neurodegenerative Effects of BMAA

For Immediate Release

 Jackson, Wyoming – October 26, 2023

 The Jackson Hole-based Brain Chemistry Labs team recently hosted a symposium for its global consortium of scientists.

The symposium served as an opportunity for researchers from around the world to unveil their latest, often not-yet-published findings and freely discuss them among their interdisciplinary colleagues.  

Dr. Paul Alan Cox presents an achievement award to Ph.D. student Katie Low for her studies of BMAA in the Greater Yellowstone Ecosystem with the Ricketts Conservation Foundation.

“We convened our extended network of neurologists, neuropathologists, chemists, biochemists, physiologists, epidemiologists, biologists, and Ph.D. students pursuing related fields. This event was particularly significant because it was our first in-person meeting since 2019,” commented Dr. Paul Alan Cox, Executive Director of the Brain Chemistry Labs.

With a focus on BMAA, a neurotoxin produced by cyanobacteria found in polluted lakes and rivers, the symposium explored how BMAA is produced and how it can be detected. BMAA has been found to cause a puzzling neurodegenerative disease among the Chamorro people of Guam, and is now considered by epidemiologists to be a risk factor for ALS. Scientists currently are attempting to determine if it could be a risk factor for Alzheimer’s and Parkinson’s disease.

 “Each person in our consortium holds an important piece of the puzzle. Bringing together these scientists from distant countries helps build a more complete picture,” Senior Scientist Dr. Sandra Banack said.

“Our common goal is to make a meaningful impact on the lives of patients suffering from these brutal diseases.”

Bo Landin, the director of a documentary on this effort called Toxic Puzzle, narrated by Harrison Ford, has recently made the film available for free public viewing at www.brainchemistrylabs.org. 

The Brain Chemistry Labs team has been testing a naturally occurring treatment option through various clinical trials, yielding promising results in terms of safety and effectiveness.

The team has also been successful in developing a diagnostic biomarker for ALS, which would accelerate diagnosis—and ultimately treatment—for patients with this serious disease.

Contact: Marya King, marya@ethnomedicine.org, 224-358-6578

Brain Chemistry Labs Elects Former California Mayor as New Board Chair

For Immediate Release

Jackson, Wyoming – October 30, 2023

Elizabeth Susan (Sue) Severson was recently unanimously elected to serve as the new Chair of the Board of Brain Chemistry Labs, a Jackson, Wyoming-based non-profit organization focused on neurodegenerative diseases.

With undergraduate degrees from BYU in microbiology and chemistry, Sue brings to her role a solid understanding of the mission, vision and goals of the Brain Chemistry Labs.  

Ralph and Sue Severson with the Orbital Trap Mass Spectrometer they gifted to Brain Chemistry Labs in 2022.

Sue succeeds Chair and Founder Bill Egan, who recently retired from his position of Chair, which he held since the organization’s creation in 2006.

“I am honored and humbled to carry on the exceptional work Bill spearheaded, and am confident that, with support from my fellow board members, we will accelerate the accomplishments of the Brain Chemistry Labs in bringing much-needed treatments to ALS, Alzheimer’s and Parkinson’s patients,” remarked Sue.

Previously, Sue served Orinda, California as a two-term mayor, and also served as President of the Orinda Union School District. Additionally, Sue has served in leadership positions in several other non-profit organizations as well as within private business.   

The Brain Chemistry Labs team is extremely grateful to Bill, its new Director Emeritus, for his bold leadership and vision since its inception.

A former Vice President of Johnson & Johnson, Bill fully supported the very early research of the Brain Chemistry Labs and helped shape the organization into what it is today.

Bill and the other board members enthusiastically endorsed Sue as their new Chair.

“Sue’s extensive and unique leadership experience, coupled with her commitment to generating new scientific discoveries to prevent, diagnose and treat neurodegenerative diseases, make her the optimal candidate to continue advancing the work of Brain Chemistry Labs, and we all are very excited to work with her in this new role,” commented Bill.

 Contact: Marya King, marya@ethnomedicine.org, 224-358-6578

Toxic Puzzle Film Explains Dangers of Cyanobacteria Blooms

Ethnobotanist Dr. Paul Cox with centenarians in Ogimi village, Okinawa.

For Immediate Release

Jackson, Wyoming – September 1, 2023

Deadly cyanobacterial blooms increasingly contaminate lakes and reservoirs.

Narrated by Harrison Ford, the documentary film Toxic Puzzle: Hunt for the Hidden Killer graphically portrays the threats of cyanobacteria to human health, including an increased risk of ALS and Alzheimer’s disease.

Jackson-based Brain Chemistry Labs scientists Paul Alan Cox and Sandra Banack sought clues to a mysterious paralytic disease that killed 25 percent of the adults in two villages in Guam.

“Research on the island was like watching a murder mystery,” Cox said.

“Who was the killer of these innocent villagers?”  

 The culprit they unmasked: neurotoxins in cyanobacteria. As the most ancient forms of life on earth, cyanobacteria produced the oxygen in the earth’s atmosphere.

However, when pollution enters lakes and reservoirs, green cyanobacterial scums and floating crusts quickly appear.

Exposure to the resulting neurotoxins can trigger serious illness and even death in people and domestic animals.

Toxic Puzzle takes viewers from Guam to Ogimi village in a remote part of Okinawa, where ALS and Alzheimer’s are unknown. The diet consumed by the 100-year-old villagers provided the scientists with clues on how to prevent and treat serious brain diseases. Studies of the Ogimi diet at the Brain Chemistry Labs here in Jackson has led to clinical trials, creating new hope for patients and their families.

 The film’s producers have provided a link for complimentary viewings of Toxic Puzzle at www.brainchemistrylabs.org.

Contact: Marya King, marya@ethnomedicine.org, 224-358-6578

Wyoming Couple Gifts Robot to Jackson Nonprofit Brain Chemistry Labs

Jackson, Wyoming – August 10, 2023

A generous gift from Dr. Denis R Lyman & Diane K Robards Lyman Foundation in Wyoming will bring rapid diagnosis of ALS much closer to the patients and their families.

Dr. Rachael Dunlop and Stewart Wood operate the new robot in the Brain Chemistry Labs.

This robot has sped up the validation process for the new microRNA ALS diagnostic test invented by the not-for-profit Brain Chemistry Labs.

The test is made from a standard blood draw in which small particles called extracellular vesicles released by the brain into the bloodstream are extracted.

Once concentrated, microRNA is extracted and sequenced.

The Brain Chemistry Labs team, led by Dr. Sandra Banack and Dr. Rachael Dunlop, discovered that a “fingerprint” of eight specific microRNAs distinguishes ALS patients from healthy people.

Using blood plasma samples from a Phase II clinical trial and the Centers for Disease Control National ALS Biorepository, the Brain Chemistry Labs team has reproduced this result four times.

 The gift of a liquid-handling robot from The Dr. Denis R Lyman & Diane K Robards Lyman Foundation moves the diagnostic test one step closer to high throughput, making it an attractive prospect for licensing by a pharmaceutical company. Automated pipetting increases the speed of analysis and reduces human error during sample preparation.

Dr. Sandra Banack holds a sample of neurally enriched exosomes extracted from an ALS patient blood sample.

 The scientists affectionately refer to the robot as “Nevada” after the first volunteer at the Brain Chemistry Labs. Nevada Robards was an early pioneer in the development of the whitewater rafting industry in Jackson Hole and was Diane Lyman’s mother.

Contact: Marya King, marya@ethnomedicine.org, 224-358-6578

How Would You Know if Neurotoxins are in Your Water?

Dr. James Metcalf in the Jackson, Wyoming laboratory. Photo credit: Dr. Paul Cox.

NEWS RELEASE 12-JUL-2023

Jackson Hole, Wyoming.

Dr. James Metcalf is pursuing a singular mission: developing a simple way that ordinary people can detect neurotoxins in their water supplies.

His polite manner and English accent belie his extraordinary professionalism.

With decades of training in elite institutions in the United Kingdom under his belt, Dr. Metcalf is recognized as one of the world’s top experts on water-borne toxins produced by cyanobacteria (also known as blue-green algae).

Travelling from the Thau lagoon in Southern France to coastal waters in Florida, Dr. Metcalf has collected water samples of green goo from lakes and estuaries worldwide for analysis at the Brain Chemistry Labs.

 “The dream is for fishermen worried about their catch or ranchers worried about the water their cattle are drinking or even for recreation boaters or swimmers to have a simple and accurate way to test for BMAA and other neurotoxins,” Dr. Metcalf explains.

The methodologies and instrumentation in the lab are world-class but far beyond the abilities of the general population. Is it possible to invent a method of detection that does not require expensive equipment and extensive training? 

The question is not academic. One toxin analyzed by Dr. Metcalf and his colleagues at the Brain Chemistry labs is of particular concern: BMAA triggers ALS and Alzheimer’s neuropathology in laboratory animals. How can individuals know if the green scum on their nearby pond or lake represents a neurological threat? 

In the laboratory, Dr. Metcalf is building an immunoassay — a means of detecting a chemical through the test tube equivalent of an allergic reaction — to BMAA. 

Immunoassays are routinely used to test for everything from COVID to pregnancy, but up to this point, no rugged and accurate immunoassays for BMAA have been available.

 “The dream is for fishermen worried about their catch or ranchers worried about the water their cattle are drinking or even for recreation boaters or swimmers to have a simple and accurate way to test for BMAA and other neurotoxins,” Dr. Metcalf explains.

“In the laboratory, we can detect BMAA at very low levels, but I am trying to produce a simple test strip that can quickly alert an individual if a water body contains dangerous substances.”

The next steps are to prepare the technology for commercial use, a somewhat daunting task for a not-for-profit research institute like Brain Chemistry Labs.

Dr. Metcalf remains optimistic. “I am fairly confident that we can demonstrate a workable prototype for our biotech partners by the end of the summer,” he says. “It is a lot of work, but the benefit for the public will be immense.”

 

For further information: james@ethnomedicine.org, marya@ethnomedicine.org

307 734-1680

“Window into the brain”: a simple blood test to diagnose ALS is both robust and repeatable.

NEWS RELEASE 12-APR-2023

Jackson Hole, Wyoming.

ALS is a rare paralytic neurological disease that can impact people in the prime of life. Delays in receiving a definitive diagnosis can be devastating for patients who typically survive only 2–5 years post-diagnosis. 

Currently, an ALS diagnosis requires multiple clinical examinations by a neurologist to determine disease progression. Unfortunately, misdiagnosis can occur, resulting in a delay of treatment. 

A simple blood test for ALS that could be administered in a doctor’s office could accelerate referrals to neurological specialists for confirmation.

Based on analysis of small genetic fragments called microRNA, such a test has been developed by scientists at the non-profit Brain Chemistry Labs in Jackson Hole.

The test accurately identifies patients with ALS, based on analysis of blood samples from seventy ALS patients and seventy controls. 

The microRNA is extracted from small particles in the bloodstream called extracellular vesicles, which protect the genetic cargo from degradation. A unique protein, L1CAM, allows concentration of particles that are diagnostic of ALS. 

The test is robust and repeatable, as described this week in the journal RNA Biology. 

“This test will assist neurologists in making a definitive and rapid diagnosis of ALS,” lead author Dr. Rachael Dunlop said. 

Early diagnosis means patients can receive treatment sooner. “Time is of the essence for ALS patients,” explains co-author Dr. Sandra Banack.

The test can also be used in clinical trials to determine the efficacy of new drug treatments for ALS––a disease for which there is currently no cure. 

The study, “L1CAM immunocapture generates a unique extracellular vesicle population with a reproducible miRNA fingerprint,” appears in the journal RNA Biology. https://doi.org/10.1080/15476286.2023.2198805

Building a Bridge Between Research & Patients.

Brain Chemistry Labs is a nonprofit research institute focused on serious brain illnesses. Our mission is to improve patient outcomes for people with serious brain diseases including ALS, Alzheimer’s, and Parkinson’s disease as well as glioblastoma.

These are considered by physicians and scientists to be among the most difficult diseases to understand and to solve.

We conduct state-of-the-art discovery research based on our small but highly qualified scientific staff in Wyoming and a broader 50 scientist consortium based at institutions throughout the world. In our scientific approach to these serious brain diseases, we focus on prevention, diagnosis, and treatment.

These connected pieces form a bridge from scientific research to better patient outcomes.

Treatments for serious illnesses.

We discovered that the naturally occurring amino acid L-serine slows protein misfolding in cell culture as well as in animal models.

We have proven in an FDA-approved Phase I clinical trial that L-serine is safe and indications that it slows the decline of ALS patients. It appears that our ongoing Phase II clinical trial of L-serine for ALS will confirm these findings.

We discovered that L-serine slows the formation of Alzheimer’s-type neuropathology in vivo.

We now seek to determine if it slows progression in Mild Cognitive Impairment—a precursor to Alzheimer’s disease—in an FDA-approved Phase II clinical trial at Houston Methodist Research Institute.

We have developed a model of Parkinson’s disease in marmosets, and are using this model to discover a new drug for Parkinson’s. Although levodopa helps Parkinson’s patients control some of their symptoms, it does not slow disease progression.

Rapid Diagnosis of ALS and Alzheimer’s Disease.

ALS patients often have to wait a year or more for an accurate diagnosis.

By analyzing blood samples from 170 ALS patients and 170 healthy individuals, we have discovered that sequences of a naturally-occurring molecule, miRNA, can assist neurologists in making a more rapid diagnosis of ALS.

Several months ago, we published our discovery of a molecule in blood samples from patients with early Alzheimer’s disease that can distinguish patients from healthy individuals at a very early stage.

Both of these discoveries will help patients and their families by allowing treatment to begin far more rapidly than ever before.

Dr. Sandra Banack analyzing blood samples in our Jackson Hole lab.

You Can Have an Impact by Making a Gift to Fight Disease.

Ralph & Sue Severson of Orinda, California, sought to use part of the proceeds from the sale of a small company they founded to improve outcomes for patients suffering from serious brain diseases. The Orbital Trap Mass Spectrometer they donated is now playing a crucial role in our analysis of new anti-glioblastoma peptides from violets.

Ralph & Sue Severson with the Orbital Trap Mass Spectrometer they gifted to BCL.

New Blood Test for ALS Promises Rapid Diagnosis

Dr. Sandra Banack at Brain Chemistry Labs preparing microRNA analysis of ALS patient blood samples.

Jackson, Wyoming — August 31, 2022

Patients with ALS, one of the most serious neurological diseases known, have been hampered by the time it takes to receive an accurate diagnosis. The period between the onset of symptoms and diagnosis averages over a year, precious time for a disease in which most patients die between 2-5 years from diagnosis. Researchers estimate that an inaccurate diagnosis occurs in 13-68% of cases.

A blood test for ALS based on microRNA—short segments of genetic material—found in particles called extracellular vesicles was developed in 2020 by scientists at the Brain Chemistry Labs. However, the precise protocols for shipping and storage of blood samples, which were maintained at -80°C, meant that many offices of doctors and neurologists would be unable to utilize the new test.

Today in an article appearing in the Journal of the Neurological Sciences, researchers from the Brain Chemistry Labs, Dartmouth Department of Neurology, and the Centers for Disease Control reported that they were able to replicate the original test with blood samples that were not collected and maintained under such stringent requirements.

Comparing blinded blood samples from 50 ALS patients from the U.S. National ALS Biorepository to 50 control participants, the genetic fingerprint of five microRNA sequences accurately discriminated between people with ALS and healthy individuals.

“We were surprised that the microRNA test worked for samples collected from various investigators under differing conditions,” said first author Dr. Sandra Banack.

Her colleagues Drs. Rachael Dunlop and Paul Cox concurred. “We expected samples would need to be stringently collected and stored,” said Dunlop. “Apparently, the extracellular vesicles shed into the blood protect their genetic cargo against different environmental conditions,” Cox said.

Verification of the new blood test is occurring at the Brain Chemistry Labs in Jackson Hole, which has applied for a patent on the test. They hope to find a diagnostic firm that can develop the test commercially for neurologists and physicians throughout the world.

Article reference: Banack SA, Dunlop RA, Stommel E, Mehta P, Cox PA. 2022. miRNA extracted from extracellular vesicles is a robust biomarker of amyotrophic lateral sclerosis. J Neurol Sci.  https://doi.org/10.1016/j.jns.2022.120396

Contacts: 

Dr. Sandra Banack, Tel: 307-734-1680, sandra@ethnomedicine.org

Dr. Rachael Dunlop, Tel: 307-734-1680, rachael@ethnomedicine.org

Dr. Paul Alan Cox, Tel: 801-375-6214, paul@ethnomedicine.org

 

We Think Differently About ALS, Alzheimer’s & Parkinson’s Disease.

Dr. Paul Alan Cox in the Jackson Hole laboratory.

One of the advantages of establishing a cutting-edge laboratory in the shadow of the Tetons is the freedom it gives our scientists to think differently about serious brain diseases.

Our focus is not on treating symptoms, but on discovering and disrupting the ultimate causes of brain diseases, particularly protein misfolding.

Our discovery of new diagnostic tests for ALS and Alzheimer’s, which promise to accelerate both diagnosis and treatment, resulted from our innovative approach.

Our testing of a naturally occurring amino acid, L-serine, to stop protein misfolds shows it to be safer, more effective, and cost-efficient than clearing β-amyloid plaques.

As a not-for-profit organization, we depend on your gifts to continue this important research. At a time of economic uncertainty, it is even more crucial that we seek new approaches to treat these most serious of diseases.

We are at a turning point, ready to make our discoveries available to patients worldwide. A gift from you right now will have a major impact.

Alzheimer’s Blood Diagnostic Test

Dr. Sandra Banack analyzing exosome test data.

At Brain Chemistry Labs, contrary to many other labs, we support the idea that misfolded β-amyloid and tau proteins are consequences rather than causes of Alzheimer’s disease.

As a result, we fear using β-amyloid and tau as blood-borne markers to diagnose and treat Alzheimer’s disease is too late in the disease process to modify the outcome.

We recently published our discovery of a unique metabolite that can diagnose Alzheimer’s at far earlier stages. Our test may even be predictive in pre-symptomatic cases.

As a way of increasing the sensitivity of the test, we will expand the number of blood samples in our cohort by incorporating blood samples from our upcoming clinical trial for Mild Cognitive Impairment, scheduled to commence in August, 2022.

ALS Blood Diagnostic Test Moves Forward with CDC Support and Triple Replication

Dr. Rachael Dunlop studies qPCR sequence data of microRNA segments for our ALS blood diagnostic

After we published our initial paper describing a diagnostic test for ALS, the Centers for Disease Control (CDC) agreed to send us 50 additional blood samples from patients diagnosed with ALS.

Comparing these to 50 blood samples from people who did not have ALS, we were extremely encouraged to find that five of the eight of our original microRNA sequences for ALS were verified. This gives us greater confidence in the sensitivity of our diagnostic assay.

To add to this, and importantly, the CDC blood samples were collected by physicians who did not have, as we did, -80°C freezers to protect the microRNA from degradation. Unlike our first 20 samples, these 50 were not collected following the stringent protocol we designed in our clinical trial.

This is important because it suggests the miRNA might be resistant to degradation, adding to the robustness and application of the assay.

The CDC has now sent us an additional 100 ALS blood samples which we will compare to 100 samples from people who have not been diagnosed with ALS.

This will confirm our ALS blood test if we get the same results.

Ultimately, we are hoping to attract the interest of a commercial diagnostic lab that has the resources to deliver this test into the hands of clinicians and patients who so desperately need a faster and more efficient way to diagnose ALS.

Validation of two diagnostic blood-marker tests for ALS and Alzheimer’s disease.

Dr. Rachael Dunlop runs our qPCR for microRNA disease diagnostics.

Our discoveries of blood diagnostic tests for ALS (based on microRNA) and Alzheimer’s disease (based on a unique metabolite) have now been published in prestigious scientific journals.

We are busily engaged in the painstaking process of validating these tests, using samples from the Centers for Disease Control for ALS, and previous samples from our Phase II early-stage Alzheimer’s trial.

We seek a pharmaceutical partner to commercialize these blood diagnostics so they can be made available to the public.

Our mission is to rapidly improve patient outcomes for serious brain diseases and thus, we want these diagnostic tests in the hands of neurologists as soon as possible.

Synthesis of an anti-glioblastoma (brain cancer) cyclotide from violets.

Synthesis of an anti-glioblastoma cyclotide from violets promises to advance our glioblastoma research by several years.

Glioblastoma is one of the most aggressive forms of brain cancer. Patients typically survive only a year after diagnosis.

We reported in the Journal of Natural Products that growth of human glioblastoma cells can be slowed by cyclotides, circular proteins extracted from violets.

By adding cyclotides, we were able to increase over eight-fold the effectiveness of the FDA-approved chemotherapy Temozolomide (TMZ).

We commissioned a state-of-the-art protein laboratory to produce a synthetic version.

Using our new Orbital Trap Mass Spectrometer, we are now testing small quantities of the synthetic molecules to ensure the same efficacy as those that occur in nature.

This synthetic approach promises to advance our glioblastoma research by several years.

L-serine, a naturally occurring amino acid, and Alzheimer’s disease

Today, a press release issued by researchers at the University of California, San Diego argued that L-serine could be dangerous for consumption.

In a letter to Cell Metabolism the researchers contested previous findings by scientists in France who found that L-serine was effective at reducing cognitive deficits in mice that exhibit aspects of Alzheimer’s disease.

L-serine is a naturally occurring amino acid synthesized by the body and is abundant in food.

While not disputing the cognitive benefits of L-serine, the San Diego team cautioned against
L-serine consumption because they found an increase of the enzyme PHGDH in mice with Alzheimer’s mutations as well as in the hippocampus of human Alzheimer’s patients.

PHGDH is the first step in a three-step enzymatic process within the brain that synthesizes
L-serine.

The San Diego researchers speculated that if PHGDH is increased, L-serine levels might also be increased. However, these researchers did not measure L-serine in the brain, nor did they perform any clinical studies. 

The Brain Chemistry Labs has been studying L-serine as a possible treatment for ALS and Alzheimer’s disease.

In FDA-approved clinical trials, no serious adverse effects have been found in patients taking
L-serine up to 30 grams per day. Furthermore, residents of Ogimi village in Okinawa, many of whom are over 100 years old, have not noted negative effects from their diet which is extremely rich in L-serine. Extensive studies of L-serine in laboratory animals have also failed to find any adverse effects of high-dose L-serine.

 The Brain Chemistry Labs does not encourage individuals outside of the clinical trials we are sponsoring to take L-serine until the FDA approves L-serine for the treatment of neurodegenerative diseases.

Additional information: 

P.A. Cox, et al. 2016. Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain. DOI: https://doi.org/10.1098/rspb.2015.2397

 P.A. Cox, J.S. Metcalf. 2017. Traditional food items in Ogimi, Okinawa: L-serine content and the potential for neuroprotection. DOI: https://doi.org/10.1007/s13668-017-0191-0

 J. Metcalf, et al. 2018. L-serine: a naturally-occurring amino acid with therapeutic potential. DOI: https://doi.org/10.1007/s12640-017-9814-x

 J. Le Douce, et al. 2020. Impairment of glycolysis-derived L-serine production in astrocytes contributes to cognitive deficits in Alzheimer’s disease. DOI: https://doi.org/10.1016/j.cmet.2020.02.004

 X. Chen et al. 2022. PHGDH expression increases with progression of Alzheimer’s disease pathology and symptoms. DOI: https://doi.org/10.1016/j.cmet.2022.02.008

Initial SWFL study finds water, air pollutants could cause grave brain disease.

By: Amy Bennett Williams

Fort-Myers News-Press
Published 12:25 pm E.T. May 2, 2022 | Updated 2:12 pm E.T. May 2, 2022.

The good news: A first-of-its-kind field study of Southwest Florida air and water didn’t find widespread cyanobacteria toxins – mostly.

The bad news: It did find several neurotoxins as well as three forms of BMAA, a neurotoxin linked to grave brain diseases.

Two of the forms were in every one of 945 analyses done over five months between last July and November by Calusa Waterkeeper volunteers and analyzed at Wyoming’s Brain Chemistry Labs.

The results were released Monday.

Researchers call the neurotoxins’ presence ubiquitous and concerning.

Health policymakers have yet to weigh in. Neither the Florida Department of Health in Lee County nor the state Department of Environmental Protection conducts cyanotoxin air sampling.

Because no study of this kind has been done, the public health implications aren’t yet clear, and more research is needed before they are, says Paul Cox, executive director of Brain Chemistry Labs.

“Are the toxins there? Yes. Are they being airborne? Yes. Are they bad news? Yes,” said Cox. “I’m sorry we don’t have firmer answers (but) citizens are really concerned about this – correctly concerned.”

Though cyanobacteria, also called blue-green algae, has long been studied, research on its human health effects is ongoing on several fronts. Universities, government agencies, and nonprofits like Waterkeeper all are looking at different aspects.

This effort is the first to sample both air and water on-site with a custom-engineered monitoring device dubbed ADAM: airborne detection for algae monitoring, designed in collaboration with algae scientists, including Michael Parsons at Florida Gulf

Coast University, a member of the state’s Blue-Green Algae Task Force.

That acute exposure can make people sick and kill dogs is not in question. Longer-term effects are less clear, but algal toxins have been linked to a number of serious illnesses, including liver cancer and neurodegenerative diseases like ALS and Parkinson’s that may take years after exposure to develop.

Also not in question: Inhalation increases the toxins’ potency, exposing them directly to the bloodstream, says Calusa Waterkeeper John Cassani. Yet there are no federal or state guidelines on exposure, he said.

That’s why his nonprofit teamed up with nonprofit Brain Chemistry Labs to do what the government doesn’t: check the air for toxins produced by cyanobacteria.

The study aims to arm the public with basic information on the toxins they may be encountering in their daily lives.

“We all have a right to know the human health impacts of harmful algal blooms,” said board president Jim Watkins.

Volunteer scientists collected air and water from eight Lee County locations, from Matlacha to Punta Rassa and up the Caloosahatchee River to Alva, then samples went to Wyoming for pro bono analysis.

It’s important to note that these results are from a period without major blooms – a relatively calm stretch, algae-wise. Had they been sampling mid- bloom the results might have been quite different, says scientist and Waterkeeper volunteer Manuel Aparicio, who led the project to develop the device.

“The goal of our work is to inform the public,” Aparicio said. “We’ve established the method ... we’ve set up a program. We’ve got rangers, we’ve got the device (and) we’re going to continue to do this.”

‘Concerning’ molecule

One neurotoxin that appeared consistently is beta-Methylamino-L-alanine, known as BMAA.

BMAA is a compound with a fixed number of carbon, nitrogen, hydrogen, and oxygen atoms said Brain Chemistry Labs scientist James Metcalf. “These atoms can be arranged in different ways resulting in different compounds with the same mass. BMAA has 2 isomers – AEG and DAB – in cyanobacteria with the same mass and numbers of atoms. Therefore, it is important to make sure that you can identify each one separately and we did this in our analyses.”

Their presence is worrisome because a recent paper strongly associated BMAA with neurodegenerative disease and concluded BMAA “most likely could cause ALS,” Metcalf said. Both of its isomers have also shown neurotoxicity in animal models.

But how much makes people sick is an open question.

“We certainly need to do more air sampling to get a better picture of our airborne exposure,” Metcalf said.

In the meantime, “People should avoid exposure to blooms and scums ... We certainly need to do more research to understand the risk of airborne exposure and this may influence future policy.”

Cox agrees. “The scientists are uncertain if the doses are enough to trigger disease,” said Cox. “We just don’t know, and it would be irresponsible of me to indicate otherwise, but I am concerned. “What I don’t want to see is a book that comes out in 10 or 20 years and has a chapter called ‘The Florida Incident.’”

New Alzheimer’s Biomarker May Facilitate Rapid Diagnosis

Blood test collection tube saying "Alzheimer's Disease"

Discovery of a unique ratio of metabolites from blood samples of early-stage Alzheimer’s patients promises to speed diagnosis of Alzheimer’s disease.

Although symptoms of advanced Alzheimer’s disease are well known, diagnosis of Alzheimer’s disease in its earliest stages requires careful cognitive testing by neurologists.

Discovery of a unique ratio of metabolites from blood samples of early-stage Alzheimer’s patients promises to speed diagnosis, allowing earlier treatments to be initiated.

“We were delighted to discover that the ratio of two molecules, 2-aminoethyl dihydrogen phosphate and taurine, allows us to reliably discriminate samples of early-stage Alzheimer’s patients from controls,” said Dr. Sandra Banack, lead author of the report in PLOS ONE and Senior Scientist at the Brain Chemistry Labs in Jackson Hole.

Dr. Sandra Banack works on the amino acid analyzer in the Brain Chemistry Labs, Jackson, Wyoming.

The blood samples were drawn from patients enrolled in an FDA-approved Phase II trial at Dartmouth Hitchcock Medical Center in New Hampshire and then shipped to the Brain Chemistry Labs for analysis. Current attempts to diagnose Alzheimer’s disease from blood samples depend on the presence of amyloid fragments, the molecules that cause brain tangles and plaques.

“At the Brain Chemistry Labs, we consider amyloid plaques to be a consequence rather than the cause of Alzheimer’s disease,” Dr. Paul Alan Cox, Executive Director of the Brain Chemistry Labs explains. “What is exciting about this new discovery is that it does not depend on amyloid and the assay can be performed on analytical equipment that is already present in most large hospitals.”

Their report, written with Alzheimer’s expert Dr. Aleksandra Stark, “A Possible Blood Plasma Biomarker for Early-stage Alzheimer’s Disease” is being published this week in PLOS ONE.

About the Brain Chemistry Labs: The Brain Chemistry Labs is a not-for-profit research institute based in Jackson Hole focused on improving outcomes for patients suffering from Alzheimer’s, ALS, and other neurodegenerative illnesses.

Contacts:
Dr. Sandra Banack, Tel: 307-734-1680, sandra@ethnomedicine.org
Dr. Paul Alan Cox, Tel: 801-375-6214, paul@ethnomedicine.org

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Epidemiological Study Finds Cyanobacterial Toxin BMAA Causes ALS

An important new article on ALS epidemiology strongly supports the hypothesis that the cyanobacterial toxin BMAA causes ALS, a devastating paralytic disease that can strike people down in the prime of life.


At the Brain Chemistry Labs, we have years of research to support our theory that BMAA is linked to ALS. Now a study from independent researchers also reports a link, strengthening our claims.

Although genetic factors have been extensively researched, only 8-10% of ALS cases are familial. Environmental factors are believed to play an important role in the remaining 90-92% of cases that are sporadic.

 Researchers at Arizona State University reviewed 1,710 scientific papers in an effort to rank possible environmental factors that potentially cause ALS. They used the Bradford Hill criteria, which is a way of measuring risk factors for disease causality.

The top supported environmental ALS risk factor emerged: the cyanobacterial toxin BMAA, which is the only environmental factor that met all nine Bradford Hill criteria. The next most likely risk factor, formaldehyde, on the other hand, only met five Bradford Hill criteria.

Dr. Paul Cox at the Brain Chemistry Labs, who was not associated with this paper, clarifies that while BMAA emerges from the new study as the best-supported causative factor, “it does not mean that exposure to BMAA or cyanobacterial toxins is the most common cause of ALS. A combination of genes and other environmental factors likely play an important role.”

The researchers concluded: “BMAA, formaldehyde, manganese, mercury, and zinc emerged as the five highest-ranked environmental factors through a combination of Bradford Hill criteria analysis and association analysis of population exposure studies.

These are the environmental toxins most recommended for the most immediate research. Due to extensive research of BMAA over the years, this analysis asserts causal criteria have been met.”

The researchers also specifically attribute population-wide BMAA exposures to consumption of contaminated seafood:

“When aligning the results from the systematic review of ranked factors with those obtained by the state-of-the-science population exposure assessment, BMAA exposures likely were derived from the ingestion of seafood harvested from waters contaminated with cyanobacteria or from ingestion of the cycad plant.”

The researchers note the importance of measuring BMAA in cyanobacterial blooms which requires trained scientists using expensive laboratory equipment.

The Brain Chemistry Labs has developed a lateral flow immunoassay, much like a pregnancy test, which promises to provide a rapid and inexpensive way to detect BMAA by water managers, fishermen, and laypeople who are concerned with cyanobacterial blooms.   

Newell ME, Adhikari S, Halden RU. Systematic and state-of-the-science review of the role of environmental factors in Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig's Disease. Science of The Total Environment. 2021 Dec 28:152504.