cyclotides

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.

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.

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."