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Posted On: 04/15/2022 2:59:22 PM
Post# of 1460
Below is copied from IHUB,
Fletch
falconer66a
Friday, April 15, 2022 2:26:40 PM
Re: sab63090 post# 357378
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Post# of 357386 Go
Blarcamesine activation of the sigma-1 protein.
Quote:
As I have been reading for quite some time: clearing Tau does NOT WORK,...
Actually, the removal of both tau and beta-amyloid protein wastes in neurons or nerves might, indeed, solve the Alzheimer’s problem. Virtually all people with neither of the those protein wastes residing in their neurons are free from Alzheimer’s symptoms. Whether or not they are direct causes, or whether they are merely incidental to other deeper Alzheimer’s causes is not clear.
In either case it has been presumed that if some mechanism could be discovered that would clear those waste proteins from neurons, the Alzheimer’s problem would be solved. In fact, that might be the case — if such a waste-clearing drug could ever be discovered.
So far, the approach has been to tweak the immune system to make molecules that will latch on to the waste proteins and thereby digest or transport them out of the cell. “Passive immunization with monoclonal antibodies (mAbs) may be able to clear toxic amyloid-ß species either directly or through microglia or complement activation, thereby halting the amyloid cascade and preventing neurodegeneration and cognitive and functional decline.”
https://pubmed.ncbi.nlm.nih.gov/24216217/
Wonderful idea. But, simply, it has never worked. Billions of dollars have been spent working up these monoclonal antibodies and testing them in either rodents or humans. In every case, consequential or disqualifying adverse events (“side effects”), with minimal therapeutic outcomes. It is abundantly clear that tweaking immunological processes fails, altogether.
But for most Alzheimer’s researchers there’s nothing else to try. Try, and try again, has been the continuing theme.
Except for Anavex Life Sciences Corp. Their approach is entirely different. Their drugs do not directly target beta-amyloid or tau wastes. Instead, they target, are ligands, of the unique sigma-1 receptor protein. When they attach (that’s what ligands do) the protein is said to be “activated” (or “agonized”). With this the protein is propitiously active, being able to control, modulate, or promote a diversity of “downstream” cellular processes; ones that don’t work well in the diseased state.
And, yes, one of those processes is “autophagy,” the cell’s housekeeping functions that grab onto, digest, and clear all of the many chemical wastes that are generated in, among others, neurons. And, yes, some of those wastes may, indeed, be beta-amyloids or tau tangles.
But, better, blarcamesine-activation of the sigma-1 receptor protein causes all sorts of downstream processes to work normally. One of the most important of these is the proper folding of enzyme proteins, making enzymes that are fully functional. With those, fewer wastes are formed, and those that do appear can be enzymatically destroyed or transported out of the cell.
That’s the deal of Anavex and blarcamesine; a unique, safe, and effective mechanism of action (MOA) unlike any other. At the top or start of all sorts of reaction cascades, it puts those in functional order; exactly what’s missing in the various CNS pathologies.
All of this is brand new. Medical researchers never heard of the sigma-1 receptor protein until they saw it in the Anavex research papers. It didn’t fit anything they knew of. It was utterly “unproven science,” with magical, too-good-to-be-true clinical results in lab rodents, utilizing an un-described, very questionable MOA. No medical professional wants to put his career on the line with such murky stuff.
Won’t it be interesting to see how medical professionals react to the upcoming Phase 3 Alzheimer’s results. Like them or not, the Anavex MOA will be entirely validated; pointing to efficacies for all of the pathologies in the Anavex pipeline. New medical technology; altogether transformative. Not only will Parkinson’s and Alzheimer’s be treated with blarcamesine, it will soon be discovered that, even better, the drug will prevent them; prophylaxis.
Finally, a few years later, it will be discovered that blarcamesine is a useful, therapeutic anti-aging agent, slowing normal aging processes and inhibiting the onset of geriatric diseases and conditions; all of which are inhibited by blarcamesine’s ability to maintain or restore youthful cellular processes, with its unique activation of the sigma-1 receptor protein.
https://investorshub.advfn.com/boards/read_ms...=168561524
Fletch
falconer66a
Friday, April 15, 2022 2:26:40 PM
Re: sab63090 post# 357378
PlusOneCoin Icon
0
Post# of 357386 Go
Blarcamesine activation of the sigma-1 protein.
Quote:
As I have been reading for quite some time: clearing Tau does NOT WORK,...
Actually, the removal of both tau and beta-amyloid protein wastes in neurons or nerves might, indeed, solve the Alzheimer’s problem. Virtually all people with neither of the those protein wastes residing in their neurons are free from Alzheimer’s symptoms. Whether or not they are direct causes, or whether they are merely incidental to other deeper Alzheimer’s causes is not clear.
In either case it has been presumed that if some mechanism could be discovered that would clear those waste proteins from neurons, the Alzheimer’s problem would be solved. In fact, that might be the case — if such a waste-clearing drug could ever be discovered.
So far, the approach has been to tweak the immune system to make molecules that will latch on to the waste proteins and thereby digest or transport them out of the cell. “Passive immunization with monoclonal antibodies (mAbs) may be able to clear toxic amyloid-ß species either directly or through microglia or complement activation, thereby halting the amyloid cascade and preventing neurodegeneration and cognitive and functional decline.”
https://pubmed.ncbi.nlm.nih.gov/24216217/
Wonderful idea. But, simply, it has never worked. Billions of dollars have been spent working up these monoclonal antibodies and testing them in either rodents or humans. In every case, consequential or disqualifying adverse events (“side effects”), with minimal therapeutic outcomes. It is abundantly clear that tweaking immunological processes fails, altogether.
But for most Alzheimer’s researchers there’s nothing else to try. Try, and try again, has been the continuing theme.
Except for Anavex Life Sciences Corp. Their approach is entirely different. Their drugs do not directly target beta-amyloid or tau wastes. Instead, they target, are ligands, of the unique sigma-1 receptor protein. When they attach (that’s what ligands do) the protein is said to be “activated” (or “agonized”). With this the protein is propitiously active, being able to control, modulate, or promote a diversity of “downstream” cellular processes; ones that don’t work well in the diseased state.
And, yes, one of those processes is “autophagy,” the cell’s housekeeping functions that grab onto, digest, and clear all of the many chemical wastes that are generated in, among others, neurons. And, yes, some of those wastes may, indeed, be beta-amyloids or tau tangles.
But, better, blarcamesine-activation of the sigma-1 receptor protein causes all sorts of downstream processes to work normally. One of the most important of these is the proper folding of enzyme proteins, making enzymes that are fully functional. With those, fewer wastes are formed, and those that do appear can be enzymatically destroyed or transported out of the cell.
That’s the deal of Anavex and blarcamesine; a unique, safe, and effective mechanism of action (MOA) unlike any other. At the top or start of all sorts of reaction cascades, it puts those in functional order; exactly what’s missing in the various CNS pathologies.
All of this is brand new. Medical researchers never heard of the sigma-1 receptor protein until they saw it in the Anavex research papers. It didn’t fit anything they knew of. It was utterly “unproven science,” with magical, too-good-to-be-true clinical results in lab rodents, utilizing an un-described, very questionable MOA. No medical professional wants to put his career on the line with such murky stuff.
Won’t it be interesting to see how medical professionals react to the upcoming Phase 3 Alzheimer’s results. Like them or not, the Anavex MOA will be entirely validated; pointing to efficacies for all of the pathologies in the Anavex pipeline. New medical technology; altogether transformative. Not only will Parkinson’s and Alzheimer’s be treated with blarcamesine, it will soon be discovered that, even better, the drug will prevent them; prophylaxis.
Finally, a few years later, it will be discovered that blarcamesine is a useful, therapeutic anti-aging agent, slowing normal aging processes and inhibiting the onset of geriatric diseases and conditions; all of which are inhibited by blarcamesine’s ability to maintain or restore youthful cellular processes, with its unique activation of the sigma-1 receptor protein.
https://investorshub.advfn.com/boards/read_ms...=168561524
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