Annovis Bio, Inc. (NYSE:ANVS) ("Annovis" or the "Company"), a clinical-stage drug platform company addressing Alzheimer's disease (AD), Parkinson's disease (PD), and other
Annovis Bio, Inc. (NYSE:ANVS) ("Annovis" or the "Company"), a clinical-stage drug platform company addressing Alzheimer's disease (AD), Parkinson's disease (PD), and other neurodegenerative diseases, today announced the publication of ANVS401's mode of action in the peer-reviewed journal Pharmaceutics with the manuscript titled "Posiphen Reduces the Levels of Huntingtin Protein through Translation Suppression".
ANVS401 (Posiphen) is an oral molecule that was shown to inhibit APP and α-Syn protein translation in previous studies. To understand how it inhibits translation, two complementary approaches were undertaken: a macro approach to examine all proteins in the cell whose translation is affected by ANVS401 and a micro approach to study the mechanism of action using molecular biology to understand and validate the binding and function.
First, the non-biased proteomics approach was applied to explore what proteins in the total protein universe were specifically downregulated by ANVS401. The results demonstrated that, in addition to the proteins already known to be reduced by ANVS401, other neurotoxic aggregating proteins – huntingtin protein (HTT) and TDP43 – were shown to be downregulated as well.
A detailed analysis of the reduction of these protein levels was conducted in five different laboratories using multiple methodologies. It revealed that the mRNAs of these proteins have a special region, an atypical stem loop, that is preserved and responsible for their translation. When this region is bound to an RNA binding protein, the mRNA is not translated. When this region is free, the mRNA is translated. In neurodegenerative conditions, the mRNA coding for these neurotoxic proteins is over-translated and produces high levels of these proteins and their onset of toxicity. ANVS401 specifically increases the affinity between this special region and the RNA binding protein, thereby preventing the mRNA from being released and translated. This leads to lower translation, lower levels of neurotoxic proteins, and less toxicity in the brain.
"These results support and cement the previous data about ANVS401's ability to reduce the translation of several neurotoxic proteins. Our rigorous approach to understanding the mode of action shows that while ANVS401 does lower the levels of more than one neurotoxic protein, it is exquisitely specific for the atypical stem loops in the mRNAs of these proteins," commented Founder, President, and CEO of Annovis, Maria L. Maccecchini, Ph.D.
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