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  • First Genetically Modified Humans; But Maybe Try Resveratrol First

    April 19, 2018: by Bill Sardi

    Modern medicine likes to pull off hoaxes, like the great cholesterol hoax that is still in play after four decades. It likes to produce expensive cures on deliver them on its own terms. Inexpensive remedies are shunned, go untested, are said to be unproven (but not disproven), and are peddled by hucksters.

    Now that you have that straightened out in your mind, you will love/loathe to hear that humans are about to be genetically edited. No, this is not an attempt to build a super-race of humans. But it is, well, a bit of an expensive scientific high-wire act that will be used to “cure” a blood disorder.

    European researchers have been given the go-ahead to splice DNA to treat a blood disorder known as beta thalassemia, an inherited disease characterized by low production of hemoglobin, the red pigment in red blood cells that carries oxygen.

    Stem cells will be harvested from thalassemia patients and then genetically edited and infused back into the patients as a stem cell transplant.

    The idea is to cut away the component that represses hemoglobin production. To do that a virus carrying a guided RNA missile will be instilled into the patient’s stem cells to produce an enzyme (Cas) that will cut away a flawed portion of DNA. To actually insert a new gene sequence, a template DNA would be required.

    The plan is to edit the aberrant gene so bone marrow can make high levels of hemoglobin again and release thalassemia patients from chronic dependency upon blood transfusions to overcome their anemia.

    Researchers are attempting to reactivate the kind of hemoglobin produced by infants. The BCL11a gene represses the fetal hemoglobin and is the target gene. This gene technology has been shown to dramatically increase fetal hemoglobin in blood stem cells in a lab dish. But now to instill them back into the blood circulation and see if they produce high-hemoglobin daughter cells.


    However, there is just one glitch in this gene-editing scheme. Altering the sequence or removal of a faulty gene altogether only addresses the inherited structural defect.

    Genetic testing now makes it possible for many people to find out the exact sequences and alterations in their DNA. However, just knowing the DNA sequences is not the whole story. Researchers write: “There is another layer of complexity added by a group of molecules called epigenetic regulators.”

    Overlooked in news headlines is that there is also a modifiable dynamic aspect of genes called epigenetics characterized by protein making. Genes that produce proteins are said to be “expressed” (switched on) and those that don’t are said to be “silenced” (switched off). Environmental factors such as temperature, radiation and food can provoke an epigenetic response.

    At the American Society of Hematology website researchers write:

    “While the impact of genomics on science and human health cannot be overestimated, DNA sequence variation represents only one part of the complex regulation of gene function. Epigenetics, which encompasses alterations in gene expression caused by mechanisms other than DNA sequence changes, also plays a significant role in phenotypic diversity and differential sensitivity to environmental stimuli… it has become increasingly clear that epigenetic mechanisms provide a completely new ensemble of therapeutic targets for treating hematologic (blood) disorders… Studies on epigenetic mechanisms have already helped identify a battery of druggable enzymes that represent potential treatment targets.”

    Another scientific mountain to climb is that more than 200 different gene mutations have been identified in thalassemia patients.

    Researchers writing in the Journal of Clinical & Diagnostic Research say: “It has been hypothesized that if the level of fetal hemoglobin increases, it compensates the need of adult hemoglobin and hence, ameliorates clinical symptoms associated with beta thalassemia major. Illation from previous studies has proved that reactivation of fetal hemoglobin with the aid of natural compounds is a better alternative therapy for patients of beta thalassemia because of its cost effectiveness and occurrence.”

    When does the gene mutation occur?

    At about the third of month of life the y-globin gene responsible for the production of hemoglobin is silenced. The epigenetic silencing of the y-globin gene suggests there is hope in reversing thalassemia by switching the gene expression (protein making) back on.

    Knowing that infants aren’t born with thalassemia and that the gene abnormality occurs after birth suggests this disease can be edited. That is why geneticists pursue their course to correct the problem.

    Actually demonstrated

    Thalidomide, a drug once used to treat nausea during pregnancy (later abandoned when it induced birth defects), has been instilled into stem cells from umbilical cord blood to favorably induce fetal hemoglobin.

    Natural molecules found in foods, such as resveratrol (grapes, wine) can serve as “natural world fetal hemoglobin inducers.” Given that there is good correlation between what happens in lab dishes (in vitro) and mammals (in vivo), the prospect of successfully using a molecule like resveratrol is high. In this regard, resveratrol (rez-vair-a-trol), a red wine molecule, produced an 8-fold increase in y-globin RNA in one study.

    In an animal study, a modest dose of resveratrol (2.4 mg/kilogram of body weight equivalent to 168 milligrams in a 70-kilogram/150-lb human) increased red blood cell production and hemoglobin levels.

    In a lab dish resveratrol shown to protect human red blood cells from oxidation and increased gene expression of y-globin and hemoglobin.

    Resveratrol was actually put to the test and produced a complete response in 52.2% of thalassemia patients, a partial response in 18.2% and null response in 15.9% of subjects. Some patients became less dependent upon blood transfusions.

    Researchers conclude: “resveratrol may be considered as a potential novel therapeutic strategy in treating βeta-thalassemia.”

    But of course, modern medicine has to make a killing on any medicine that quells any disease, so pharmacologists have attempted to re-engineer resveratrol to produce a patentable synthetic analog (look-alike molecule) that will cost a fortune.

    Why isn’t resveratrol getting all the news headlines instead of gene therapy?

    Will thalassemia patients be freed from dependency upon blood transfusions by costly genetic or economical epigenetic therapy?

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