Can We Transform the Diagnosis & Treatment of ALS?

In 1874, Jean-Martin Charcot described a devastating paralytic illness which we now call ALS.

ALS cuts down people in the prime of their lives.

Only two FDA-approved drugs exist for the treatment of ALS, and neither significantly slow disease progression.

We have focused on the early diagnosis and treatment of ALS.

We discovered a molecular fingerprint of ALS, which will allow neurologists to definitively diagnose ALS based on a single blood draw. We extract microRNA from exosomes—microscopic packages of genetic material—in the blood sample. The unique assemblage of microRNA identifies ALS patients.

Currently, many patients have to wait a year or more to receive an ALS diagnosis. This new diagnostic test will allow patients to begin treatment much earlier.

Our advanced clinical trials of the naturally occurring amino acid L-serine are promising.

Hopefully, this combination of a diagnostic and a treatment package will be attractive to a pharmaceutical partner who can conduct the larger clinical trials that will be needed.

Dr. Sandra Banack prepares an ELISA plate to measure exosomes.





Happy Birthday Yellowstone National Park!

Grand Prismatic Spring in Yellowstone National Park. Photo credit: Dr. Paul A. Cox

One hundred and fifty years ago today, on March 1, 1872, the first National Park in the world, Yellowstone was created by the United States Congress and signed into law by President  Ulysses S. Grant.

National parks, termed by documentary filmmaker Ken Burns as “America’s Best Idea” have continued since that time to be created, including the 50 th National Park of the United States in American Samoa, in which our Executive Director Dr. Paul Alan Cox, played a key role.

Happy Birthday, Yellowstone!

National Park of American Samoa. Photo credit: nps.gov

Compound from violets may help fight glioblastoma

NEWS RELEASE 26-JAN-2022

BRAIN CHEMISTRY LABS

A circular peptide derived from violets could lead to new approaches in treating glioblastoma, a highly aggressive form of brain cancer.

(Jackson, Wyoming—January 26, 2022) – A circular peptide derived from violets could lead to new approaches in treating glioblastoma, a highly aggressive form of brain cancer.

Researchers report that cyclotides, small circular proteins produced by violets increase the power of TMZ, a chemotherapeutic agent, in killing human glioblastoma cancer cells. 

Glioblastoma is a fatal type of brain cancer of adults and children with a median survival time of 9-16 months from diagnosis. Half of the tumors are resistant to the only FDA-approved treatment, TMZ, and the remainder quickly evolve resistance to this chemotherapy. Combining cyclotides with TMZ can increase the ability of TMZ to kill glioblastoma cells up to eight-fold, researchers report.

“We think we are on a path that could lead to better treatment of glioblastoma in the future,” reports Dillard University Professor Samantha Gerlach, lead author of the report published last week in the Journal of Natural Products. 

The biggest hurdle faced by researchers working in the laboratories based in Wyoming is extracting enough of the compounds from violets to test. Kilograms of violets are needed to yield a tiny dose.

“Our cell culture studies, though encouraging, are far from being useful in a clinical setting,” cautions Dr. Paul Alan Cox, Director of the non-profit Brain Chemistry Labs in Jackson Hole. “Just extracting enough cyclotides to test in mice will take months.”

Despite these technical obstacles, the research team remains undaunted. “Patients, particularly children, diagnosed with glioblastoma have few options,” says Dr. Samantha Gerlach. “Our goal is to eventually provide new hope to glioblastoma patients and their families.”

Find the original research here

Novel Glioblastoma Treatment – New Publication

Cyclotides are a group of compounds found in violets

Together with visiting scientist Dr. Samantha Gerlach, we found that circular proteins called cyclotides extracted from violets could allow us to reduce eight-fold the dose of TMZ, a chemotherapeutic agent for glioblastoma.

This would slow the evolution of drug resistance of brain cancer cells to TMZ. We are now trying to purify a sufficient dose of the cyclotide to test in mice.

Our paper detailing our discovery will soon appear online in the Journal of Natural Products.

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.

Protein Misfolds Spread Like Prions in Alzheimer’s

The addition of L-serine to the diet of mice restored their memory

We believe protein misfolding to be the ultimate cause of Alzheimer’s, ALS, and other neurodegenerative diseases.

We discovered that environmental toxins such as BMAA can trigger protein misfolding.

How do protein misfolds spread from neuron to neuron? L-serine is produced within astrocytes, which help neurons.

Recently, a French team found that mice which cannot produce L-serine in astrocytes have memory problems. The addition of L-serine to their diet restored their memory.

Deficiencies in L-serine production within astrocytes may allow protein misfolds to propagate within the brain.

A New Approach to Parkinson’s Disease Therapy

David Long

Lewy bodies, formed from misfolded α-synuclein protein, are the neuropathological feature of Parkinson’s disease. While levodopa can help control symptoms, no current Parkinson’s medication slows disease progression.

 We attempted to produce Lewy bodies in vivo but did not have enough funds to continue the experiments. Enter Ty and Sue Measom of Logan, Utah, and Fred and Candy Berthrong of Providence, Utah who provided a generous gift to complete the study in which we found that BMAA triggers Lewy bodies in marmosets.

 We were unable to begin a second study until the philanthropic torch was picked up by Robert and Robin Paulson and Stan and Mary Seidler of Jackson Hole. They provided the lead gifts to determine if L-serine or L-tyrosine can slow Lewy body formation.

A generous pledge from David and Lisa Long of Lake Forest, Illinois allowed us to accelerate the project. Our colleagues at NeuroScience Associates in Tennessee assisted us by giving a significant discount on the regular fees for state-of-the-art sectioning and staining of the tissues. We still have $100,000 to raise to finish the project but are proceeding at full speed.

Because of the generous donors who helped us, including Bobbie Sweet, John Madigan, and James and Ellen Walton, we will have the final results in February 2022. If successful, this new drug will remain a lasting legacy for David Long who passed away on September 19, 2021.

Brain Chemistry Labs Welcome Dr. Samantha Gerlach to its Jackson Laboratories

Dr. Samantha Gerlach in Grand Teton National Park

An assistant professor at Dillard University in New Orleans, Dr. Gerlach joined the Brain Chemistry Labs team this summer to focus on active ingredients in native plants and their potential for new drug therapies for brain diseases, particularly glioblastoma.

 Brain Chemistry Labs’ Executive Director, Dr. Paul Alan Cox, and Dr. Gerlach both recognize the important connection of plants and their medicinal properties. In fact, Dr. Gerlach has spent a significant amount of time looking at violets.  She has hunted violets from Sweden to Samoa, not because of their beauty – which she admires – but because of their medicinal potential for new drugs.

 In her previous work, Dr. Gerlach learned that “violets produce a category of anti-cancer peptides known as cyclotides which in structure, resemble circular knotted or tangled puzzles.”

Dr. Gerlach goes on to explain that, “the anti-cancer activity is found in the knots, formed from linked sulfur molecules that give cyclotides a sharp point that can be used to puncture cancer cells. All too soon, cancer cells evolve resistance, so chemotherapy stops working. Cyclotides can punch pores into resistant breast cancer cells, restoring their susceptibility to chemotherapy."

Brain Chemistry Labs’ Executive Director Receives Prestigious Medal from the Garden Club of America

Dr. Paul Cox, Executive Director, Brain Chemistry Labs.

Dr. Paul Cox, Executive Director of the Brain Chemistry Labs, received one of the highest honors bestowed by The Garden Club of America (GCA), the Eloise Payne Luquer Medal for his scientific research related to ALS and Alzheimer’s disease. The medal was presented at the GCA’s annual meeting in Boston on May 19, 2019. According to GCA, “The Eloise Payne Luquer Medal is awarded for special achievement in the field of botany that may include medical research, the fine arts, or education and was presented with gratitude to a renowned ethnobotanist, consummate scientist, teacher, environmentalist, and activist, Dr. Paul Alan Cox. His compassion combined with his rigorous scientific methods are improving our world.”

GCA awards up to 10 National Medals a year to “nationally and internationally recognized leaders in their fields of study or achievement” and describes the medal winners as “visionaries all, passionate and influential, these men, women, and organizations have left a profound and lasting impact on the issues that are most important to the Garden Club of America.”

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Brain Chemistry Labs focus on Florida blooms.

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Dr. James Metcalf samples the waters of Florida

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. READ MORE.

Brain Chemistry Labs' Movie Selected for Newport Beach Film Festival

It was a successful world premiere of the documentary Toxic Puzzle, featuring Brain Chemistry Labs’ Paul Alan Cox, his team in Jackson Hole and collaborators from around the world.

After the screening, the film’s director Bo Landin and Paul Cox answered questions in a Q&A. The film was also selected for the Earth Day Film Festival, and has been picked for review at the upcoming IMPACT Docs Awards.

Following the world premiere the film was broadcast in Sweden and Norway, attracting some 600,000 viewers and an interesting live online chat in Sweden and a very active ongoing discussion in social media inNorway. 

The film can now be streamed or downloaded from multiple online stores like Amazon, iTunes, Google, Microsoft and VUDU.

Dr. Paul Alan Cox Gives TED Talk at Jackson Hole

Paul Alan Cox is a Harvard Ph.D. who has searched for new medicines from plants used by traditional healers in the Pacific and Southeast Asia. For these efforts TIME magazine named him one of 11 "Heroes of Medicine." His efforts in preserving island rain forests were recognized with the Goldman Environmental Prize.