EGCG AND IKAP – WHAT WE HAVE DISCOVERED:
The continuing search for compounds that enhance the production of the functional IKAP protein revealed that epigallocatechin gallate (EGCG), a molecule found in green tea, corrects the aberrant splicing (caused by the FD mutation) of IKAP RNA, allowing for the increased production of the functional IKAP protein. Furthermore, the treatment of cells derived from individuals with FD with a combination of tocotrienols and EGCG was observed to result in a synergistic (more that additive) increase in the levels of functional IKAP protein produced in the FD-derived cells. These laboratory findings support the therapeutic use of the combination of tocotrienols and EGCG in individuals with FD.
EGCG AND GENISTEIN AS A COMBINED TREATMENT – WHAT WE HAVE DISCOVERED:
In the laboratory, we have had an ongoing program that is designed to identify naturally occurring, non-toxic, readily available compounds capable of increasing the amount of IKAP protein in individuals with FD. Our latest discovery is that two compounds commonly found in soy, genistein and daidzein, correct the aberrant splicing of IKAP RNA that occurs because of the FD mutation. These compounds very effectively increase the amount of IKAP protein produced in cells of individuals with FD. We have also observed that genistein affects the RNA splicing process in neuronal cells (where the effects of FD are manifested the most), which is very significant. In addition, the combined treatment of FD-derived cells with genistein and EGCG results in an approximately five-fold increase in the amount of functional IKAP RNA produced in the FD-derived cells. While the amount of IKAP RNA produced in FD-derived cells is important, what really matters is how much of the functional IKAP protein is produced in these treated cells. We have observed that the combined treatment of FD-derived cells with genistein and EGCG results in the production of IKAP protein levels that are the equivalent to that produced in normal human cells.
EGCG ADMINISTRATION IMPROVES AUTONOMIC STABILITY DURING SURGERY – WHAT WE HAVE DISCOVERED:
The scientific literature is replete with publications that document the extreme cardiovascular and autonomic instability observed in FD patients undergoing surgical procedures. Upon observing this instability in FD patients on the day of surgery, surgical teams have refused to perform surgical procedures on these patients. A planned surgical procedure on an FD patient who was ingesting tocotrienols and EGCG-containing green tea extract provided an opportunity to characterize the impact of these IKAP-enhancing compounds on cardiac and autonomic stability during and after surgery. As this patient had previously undergone a surgical procedure prior to beginning tocotrienol and green tea extract ingestion, a comparative analysis of this patient’s response to the two surgical procedures was performed. This analysis clearly revealed that the uninterrupted ingestion of the tocotrienols and green tea extract resulted in a dramatic improvement in the cardiac and autonomic stability of this patient.
This study, which was published in the journal Anesthesiology, recommends the uninterrupted administration of tocotrienols and green tea extract to FD patients who are scheduled to undergo a surgical procedure. While ingestion of the tocopherol form of vitamin E has been reported to impair the blood clotting process, no such effect of the related tocotrienols was observed in this patient. A study of the blood clotting efficiency in a group of FD patients ingesting 600 mg of tocotrienols daily revealed no reduction in the blood clotting response (manuscript in preparation).