Posted on 01/05/2022 9:15:14 AM PST by ConservativeMind
A folic acid-like drug, L-methylfolate, when administered alongside the standard therapy for patients with recurrent glioblastoma, changed a DNA process within their brain tumors, according to results from a phase 1 clinical trial.
The researchers showed for the first time that the DNA methylome of these brain tumors can be reprogrammed. Stephen Clark, Ph.D. said that this is the first time DNA methylome reprogramming has occurred with any solid human tumor.
The DNA methylome is one aspect of the epigenome; the epigenome is a modification of DNA and proteins in a cell that is influenced by the environment. DNA methylation is one such modification, where methyl groups are added to DNA and is a mechanism that controls gene expression, including the silencing or activation of genes related to cancer.
…the patients treated with the folic acid supplement L-methylfolate had a median overall survival of 9.5 months, compared to the typical median overall survival of 8.6 months. One of the patients is still alive.
In this trial, the researchers assessed bevacizumab, a monoclonal antibody that prevents tumor blood vessels, augmented with L-methylfolate. The patients also received temozolomide, a chemotherapeutic agent. L-methylfolate was well tolerated, with no toxicities reported.
"Epigenetic reprogramming is not a new concept; for instance, a DNA methyltransferase inhibitor treatment (5-Azacytidine) has been studied and is approved for the treatment of some leukemias. What is exciting about this work is that L-methylfolate, acts oppositely to 5-Azacytidine; it increases the availability of the active folate for the DNA methyltransferases. Consequently, it could remethylate and repress genes activated during tumorigenesis," said Lucas Salas, MD, Ph.D.
"Further, we observed changes in the level of DNA methylation in the tumors of those receiving L-methylfolate, suggesting that L-methylfolate not only crosses the blood-brain barrier, but it seems to modify the tumor epigenetic landscape actively."
(Excerpt) Read more at medicalxpress.com ...
My wife and I recently cut out our folic acid supplement and food sources in favor of a multivitamin with only active forms of B-vitamins, which eliminates conversion steps that may not be properly working.
The “methylation” described is an action some active forms of B vitamins can help achieve, but may more commonly be performed in the body by other processes via choline (egg yolks) betaine/trimethylglycine (beets), and other food-based sources.
Epigenomic DNA methylation is one of the reasons every cell in your body can have the same DNA in the nucleus and yet can differentiate into all the functionally specific cells to make muscle, blood, liver, brain, etc. This differentiation is communicated between cells as they exchange sacs of information molecules following a shared template that is yet to be fully understood.
The exact gene sites where methylation takes place are very complex and any drug that targets one site must be specifically tailored to only modulate the desired gene and not affect other cells in the body.
This is why I’m skeptical of any broad methylation therapy that could have significant side effects until we fully understand how to localize the delivery of the molecules to the right DNA location. This is where CRISPR guide molecules may be useful to only deliver the methylation at the site that matches a specific DNA site. This therapy needs a rifle, not a shotgun.
For my brother and I, when we take folic acid, it seems to make our emotions more intense.
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