Analysis by Buzzword
There was a poignant visualization of what science is really like rendered by Stanisław Lem (science fiction writer). In a story, a strange machine created science; groups of people in white lab coats appearing to read and write papers, quarrel about them, burn them, shout and carrying them above their heads in excitement, all against their detractors etc, etc. (the human element of something abstract)
Science when it percolates to the public, relies on buzzwords, and every new one is better than the one before it. You have to be deep in the weeds to read papers and understand all the connections and implications which would drive the next set of papers to be written, so I relied on buzzwords, or rather I ask myself where are their limitations.
On many forums there is a cornucopia of posts citing ANAVEX 2-73, and Precision Medicine together, with admixture of the resulting euphoria . I have lived through many “revolutions” in science and industry, which ended with those buzzword being forlorn and missing from public memory after few years. Do you remember superconductivity in room temperature ( 1980’s ) – Oh! the world was supposed to be so different from the one we have today!
On July 25th, AVXL revealed that some common variations of two genes were correlated with response to ANAVEX 2-73. The variants of gene of related to morphology of SIGMAR1 receptor is no brainer since ANAVEX 2-73 binds to it and any changes can either attenuate the effect or strengthen it. I do not think that getting to the bottom of interaction between the ligand and drug is on agenda of Dr Missling at this moment – way too costly.
Nobody knows why ANAVEX 2-73 has the effect on SIGMAR1 and that might be a saga of its own. I do not know whether anybody mapped (3D structure) of the ligand or any drug with affinity to it. The market is yawing because many tried to affect the ligand and got nowhere. As a consequence, ANAVEX 2-73 will come as a surprise to the pundits and investing public alike.
Once this happens number of ventures will start looking into interaction of the ligand and drug to copy the interaction, and not the drug, to circumvent the patent.
The second gene called out is COMT, its variations are connected to tradeoffs between ability to perform under stress and cognition (ah! heterogeneity of human race and evolution!). The researches at smaller companies spread in all directions, in search of paths less taken, so some pursuit now the connection between mental stress and Alzheimer via inflammation.
In the light of involving in the mix inflammation, (a splendid buzzword by itself) one can only mention that two main approaches to tackling Alzheimer besides current benjamins of Big Pharma; Amyloid β and Tau, which are inflammation and mitochondrial health.
So what is in perfect world Precision Medicine? A patient’s genomic and phenotype profile is used to make drugs to seamlessly interact with both to restore health. With ~60,000 genes and phenotype multiplying this way high because of epigenetic filter on activation of genotype, I think we are way over our heads, with what current status of medicine can handle.
The effort by ANAVEX to use the genetic analysis is just a foray into complex and vast field Precision Medicine, but somebody has to make first step in thousand step journey.
Please, curb your enthusiasm and be ready to reignite it again!