Differences

This shows you the differences between two versions of the page.

--- home:publications:marshall_days_of_molecular_medicine_2006 [09.05.2010] – paulalbert
+++ home:publications:marshall_days_of_molecular_medicine_2006 [07.04.2022] (current) – external edit 127.0.0.1
@@ Line 1: / Line 1: @@
 ~~NOTOC~~
-====== Poster - Molecular static and dynamic analyses reveal flaw in murine model used by US FDA to detect drug carcinogenicity ======
+====== Poster - VDR Nuclear Receptor competence is the key to recovery from chronic inflammatory and autoimmune disease ======
 **Type:** Abstract presentation\\
 **Presented by:**  Trevor Marshall, PhD\\
-**Conference:**  [[http://www.nature.com/nm/meetings/dmm2007/program.html|Days of Molecular Medicine 2007]]\\
+**Conference:**  [[https://www.nature.com/nm/meetings/dmm/index.html|Days of Molecular Medicine 2006]]\\
-**Location:**  Harvard University\\
+**Location:**  Karolinska Institute\\
-**Date:**  2007\\
+**Date:**  2006\\
-**Additional content:** [[http://autoimmunityresearch.org/transcripts/dmm2007-harvard.pdf|poster]]
+**Additional content:** [[https://autoimmunityresearch.org/karolinska-handout.pdf|PDF of Poster]]
-===== Abstract =====
-The US FDA currently accepts carcinogenicity studies of
+===== Abstract =====
-pharmaceutical drugs based on murine models. In addition to 6 month
-studies with p53(+/-) and ras.H2 transgenic mice, lifetime studies
-(typically 2 years) in WT mice or rats are also considered as evidence
-that a drug lacks carcinogenic activity. This model is not always
-exhaustive. For example, during the acceptance testing of the ARB
-Olmesartan((FDA CDER: NDA-21-286, Sankyo Pharma Inc Available from URL
-http://www.fda.gov/cder/foi/nda/2002/21-286_Benicar.htm)), possible carcinogenicity observed in hamsters was not
-able to be duplicated in rats, or in transgenic mice. We have previously
-used the static molecular modeling of AutoDock to demonstrate that
-Olmesartan has agonostic activity in the PDB:1DB1 model of the
-human VDR Nuclear Receptor((Marshall TG: VDR Nuclear Receptor Competence is the Key to Recovery from
-Chronic Inflammatory and Autoimmune Disease.
-Abstract presentation, DMM2006.)), while it has antagonistic activity in
-the PDB:1RK3 model of the rat VDR. This agonism has now been
-confirmed with Molecular Dynamics, using GROMACS. The murine
-VDR indeed lost its ability to bind the DRIP 205 co activator when
-Olmesartan was the ligand, while the human VDR was activated by
-Olmesartan similarly to its native ligand (1,25-dihydroxyvitamin-D).
-Since the VDR is believed to express 913 genes(({{pubmed>long:16002434}}))
-This video was created using the GROMACS Molecular
-Dynamics software on a small computing cluster assembled
-from PCs based on Core-2-duo CPU technologies. The
-difference in steady-state ligand conformation between
-human and rat VDR can clearly be seen at
-http://autoimmunityresearch.org/dmm2007/dmm2007.ram, many of which are
-known to be associated with cancer pathogenesis, good homology
-between human VDR, and the animal model VDR, is exceedingly
-important.
-==== Conclusion ====
+The VDR Nuclear Receptor is at the heart of the human innate immunity, responsible for TLR2, TLR4, CAMP TACO and IL2 expression [1]. During Th1 immune challenge, the VDR is activated by the endogenous secosteroid 1,25 dihydroxyvitamin D. We have previously described how intra-phagocytic bacterial pathogens are responsible for much chronic inflammatory disease [2,3], and our phase 2 study results have confirmed this pathogenesis. In order to induce recovery from chronic inflammatory disease, it is necessary to restore VDR function by removing all exogenous sources of the secosteroid we call ‘Vitamin-D,’ and dampen down over-exuberant VDR activity, for example with the ARB Olmesartan[1]. This enables the immune system to recognize the pathogens.
+RESULTS: To date we have demonstrated recovery from Hashimoto’s Thyroiditis, Rheumatoid Arthritis, Sarcoidosis, and an assortment of chronic inflammatory diagnoses. This breakthrough is the result of a collaboration between molecular scientists and a disparate group of innovative physicians, facilitated by the Internet. However, the widespread application of this pathogenic understanding will require meticulous translation of the molecular science into conventional clinical precepts.
-The murine environment is inadequate to accurately
-model drug carcinogenic activity in humans. A species should be
-chosen which has a VDR LBP homology closer to that of man. AutoDock
-and GROMACS molecular analyses are useful in resolving any
-remaining anomalies in the observed data.
-{{tag>posters videos Trevor_Marshall_PhD DMM murine_model 2007}}
-===== References =====
-{{tag>posters Trevor_Marshall_PhD 2007}}
+{{tag>posters Trevor_Marshall_PhD 2006}}

home/publications/marshall_days_of_molecular_medicine_2006.1283692843.txt.gz · Last modified: 09.05.2010 by paulalbert