3 ms·
So how does it work... The second enzyme mentioned is one possessing acetaldehyde dehydrogenase activity, ALDH2 being the primary actor. This would not be a va
by tomkinstinch 14y ago
So how does it work...
The second enzyme mentioned is one possessing acetaldehyde dehydrogenase activity, ALDH2 being the primary actor. This would not be a vaccine in the traditional sense since it would not cause ethanol to prompt an immunological response.
The closest paper I could find is this one from 2010, that describes the mechanism of action[1]:
"a long-term inhibition of ethanol consumption by reducing ALDH2 levels by the administration of vectors that code for anti-aldh2 antisense RNA molecules that inhibit aldh2 gene expression"
Pretty cool; they are using a viral vector to introduce complementary RNA that binds to the mRNA responsible for translation of ALDH2, directly down regulating expression of ALDH2. This reduces the number of ALDH2 enzyme molecules available to interact with acetaldehyde by reducing the number created (compared to disulfiram, which is a competitive inhibitor of ALDH2 itself). It seems the antisense RNA used targets the mitochonrial isoform of ALDH2, mimicking the effect of the "natural" mutation. I wonder if it has cross specificity adequate to inhibit expression of the cytosolic isoform as well.
Acetaldehyde is not the only substrate for ALDH2 however. Glyceryl trinitrate (nitroglycerin) and amyl nitrite are also metabolized by ALDH2, so this treatment might not be wise for those taking glyceryl trinitrate for a heart condition or amyl nitrite for cyanide poisoning/heart. It looks like the cells in coronary arteries mainly use cytosolic ALDH2 to metabolize glyceryl trinitrate[2] though, so if this "vaccine" only inhibits the mitochondrial isoform it may not interfere with the effectiveness of these other drugs.
1. (Martinez, et al.) http://www.captura.uchile.cl/bitstream/handle/2250/11147/Martinez_V.pdf?sequence=1 http://www.captura.uchile.cl/bitstream/handle/2250/11147/Mar...
Viral vectors for the treatment of alcoholism: Use of metabolic flux analysis for cell cultivation and vector production.
2. (Beretta, et al.) http://www.ncbi.nlm.nih.gov/pubmed/22207712 http://www.ncbi.nlm.nih.gov/pubmed/22207712 Vascular bioactivation of nitroglycerin is catalyzed by cytosolic aldehyde dehydrogenase-2.