Glioblastoma is one of the most deadliest brain diseases known, with over 45% of brain cancers being gliomas. Glioblastoma is extremely dangerous, affecting both children and adults, with most patients perishing within 9-12 months of diagnosis. Surgery to remove tumors is particularly difficult, especially in children. To add to this, only roughly half of glioblastoma patients respond to the FDA-approved chemotherapy Temozolomide (TMZ), and even for those patients, the cancer cells rapidly evolve resistance.
While the exact cause of the condition is unknown, it is associated with genetic disorders like neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome. Glioblastoma is 1.6 times more common in males than in females, and it is usually found in the supratentorial region of the brain, which includes the frontal, temporal, parietal, and occipital lobes. In America, the rate of incidence is 3.19 per 100,000 people, with over 300,000 cases being diagnosed annually around the World making glioblastoma the most common primary malignant brain cancer. Unfortunately, less than 7% of glioblastoma patients will survive for more than 5 years.
Hope from an unexpected source
The Brain Chemistry Labs in Jackson Hole, Wyoming has taken an innovative approach to glioblastoma treatment based on cyclotides, a small circular peptide extracted from violets, which is offering a glimmer of hope.
This suite of peptides is only found in minuscule concentrations in violets and they look “like floppy frisbees,” says senior author Dr. Samantha L. Gerlach. “They have been found active in the test tube against certain types of human cancer cells.”
“While kalata B1 commonly occurs in violet species, extraction from plant material yields only minuscule amounts,” Gerlach states. “Working day and night for months, the minimal quantities we obtain are insufficient for clinical research.”
Synthetic production of the peptide
The lab in collaboration with CSBio has found a way to produce synthetic versions of the violet’s cyclotides (kalata B1) to use in their research and has demonstrated that in test tubes these cyclotides can increase the power of TMZ to kill glioblastoma cells by eight-fold. Their study has been published in Biomedicines.
“Our cell data suggest that we can now move forward with the synthetic version in mice models,” Dr. Rachael Dunlop at the Brain Chemistry Labs stated. This next step of testing in mice will occur in Vienna, Austria.
Working with their collaborator Dr. Christian Gruber of the Medical University of Vienna, the effectiveness and safety of the synthetic molecules determined marks a step forward to moving to human clinic trials.
While this does offer a glimmer of hope, the lab is cautious about overstating the significance: “We are still a long ways from clinical trials, but now the way is clear to determine if it might be safe for further testing,” said Brain Chemistry Labs Director Dr. Paul Alan Cox.
According to the lab, “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.”
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References/Sources/Materials provided by:
https://brainchemistrylabs.org
https://brainchemistrylabs.org/news-blog/tag/Samantha+Gerlach
https://pubmed.ncbi.nlm.nih.gov/35044783/’
https://www.mdpi.com/2227-9059/12/10/2216
https://braintumor.org/events/glioblastoma-awareness-day/about-glioblastoma/