A blood test to diagnose ALS.

A blood test to diagnose amyotrophic lateral sclerosis (ALS) could be widely available within two years.

Currently, ALS is diagnosed through a clinical examination by a neurologist but distinguishing it from other neurological diseases requires tracking symptom progression.

 This is problematic, as the average survival time in ALS is approximately three years, meaning many patients deteriorate significantly before receiving a definitive diagnosis.

Initial misdiagnosis rates range as high as 68%, delaying treatment and causing patients to be passed between specialists, increasing anxiety, unnecessary interventions, and costs.

A simple blood test for ALS would be a game-changer. It would speed up diagnosis, reduce anxiety, lower costs, and support the development of new drugs. Given the high misdiagnosis rate, a negative result would also be highly valuable.

Extracellular vesicles are nano-sized particles that circulate in the blood, are secreted by all cells, an contain microRNA. 

Researchers at the Brain Chemistry Labs in Jackson, Wyoming, reported today in Brain Communications that they have identified an ALS-specific biomarker, an “ALS fingerprint,” in the blood. The biomarker of eight microRNAs (miRNAs) can be detected via a simple blood draw.

Using next-generation sequencing and real-time PCR, the team analyzed blood samples from patients with ALS, Primary Lateral Sclerosis (PLS), Parkinson’s disease (PD), and healthy individuals.

The eight microRNA ALS fingerprint accurately detects ALS with as high as 98% accuracy and can separate ALS from PLS and PD.

“Faster diagnoses will allow for earlier treatment, which will improve patient outcomes,” says Sandra Banack, lead author of the study.

To confirm its reliability, the biomarker was tested across four different patient groups, in two labs, with various technicians and collection methods. The ALS fingerprint consistently produced reliable results.

Researchers believe this blood test could assist neurologists in diagnosing ALS and complement current clinical assessments.

Dr. Paul Alan Cox, Executive Director of Brain Chemistry Labs, hopes to secure a diagnostic company partnership and make this test widely available to neurologists within 18 to 24 months.

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Brain Chemistry Labs is a 501(c)(3) not-for-profit organization in Jackson, Wyoming, that seeks to discover new ways to prevent, diagnose and treat ALS, Alzheimer’s, Parkinson’s and other serious brain diseases.

The Brain Communications paper, “A microRNA diagnostic biomarker for amyotrophic lateral sclerosis” (DOI 10.1093/braincomms/fcae268) can be accessed here.

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.’”

Like Origami Paper, Proteins Must Be Folded Correctly

In Origami, 2-D pieces of paper can be folded into 3-D masterpieces. 

A protein is a linear sequence of amino acids linked together through peptide bonds. Proteins differ in the sequence of the twenty different amino acids that our cells assemble, and in their length. However, to function properly, the 1-D protein has to be correctly folded into a 3-D structure.

Hemoglobin (below) is the oxygen-carrying protein in our bloodstream, but it cannot carry oxygen unless its linear structure is folded properly. When a protein misfolds, it becomes toxic. Unlike other cells in the body, neurons cannot dilute the toxin by rapidly dividing. Misfolded proteins clog up transportation systems in neurons and cause them to die.

Each of the progressive neurodegenerative diseases is characterized by different proteins which misfold. Our strategy in developing new therapies for ALS, Alzheimer’s, and Parkinson’s is to find drugs that stop protein misfolding. We discovered that the amino acid L-serine helps to prevent protein misfolds.