RE: A take on the Blanco ReportThis was a response to this article I thought worth sharing. Many of the responses are interesting
Dr. KSS MD PhD
My intent in commenting on ProMIS is not to make it look risible (I don’t question its sincerity in its approach and its belief in the authenticity of its work) but simply to caution investors and safeguard against capital losses.
I see several issues about its approach that are not necessarily problems unique to ProMIS:
(1) the amyloid hypothesis has serious deficits. Science cannot even answer why amyloid is elaborated, though we have made contentions in early commentaries about its origin.
(2) Two major theories of the ailment have gained considerable momentum: these would be the dampened synaptic transmission hypothesis and the RAGE receptor-driven neuroinflammation hypothesis. The Candida torulopsis hypothesis is strong but needs further testing by a clinical antimicrobial trial.
(3) people keep forgetting that monoclonal antibodies are possibly the worst reagents to be using to go after Alzheimers. They are being used as stoichiometric binding agents in pursuit of amyloid occupancy. But does this make sense? Satisfying establishment of the mere extent to which mAb’s, among the largest molecules the body sees, can cross the blood brain barrier is lacking. People also forget that IgG is complement-fixing, and thus evokes strong secondary inflammatory responses; ProMIS I admit is using an IgG4 that may have abated complement-inducing activities though I’d need to see data to be sure. But even if complement is not activated, there is the issue of Fc receptor binding after antigen engagement, and Fc receptors abound….on macrophages, other immune cells, even on platelets. Thereby CNS inflammation is further stoked. An anticalin would be vastly more ideal in pursuit of finding an anti-amyloid reagent, though I doubt any solution lies in the amyloid approach to things.
(4) no disease being pursued by biotech has a greater gulf between in vitro and in vivo investigative mechanisms; a cell culture model of AD that is genuinely relevant on all axes is impossible, and no definitive animal model exists. We cannot be invasive (ie, brain biopsies) in assessment of the histopathology, which radically alters itself upon death. A true solution may await further development of miniature CNS agglomerations ex vivo attained by 3-D bioprinting or by signalling of stem cells , along with tactics to replicate presence of an immune system.
(5) $CWBR has a mitochondrially elaborated peptide that reverses amyloid induced neurotoxicity and neuron paucity. The mechanism is only partly known but tends to undermine the amyloid hypothesis. Rather, I regard the best theory of AD is that it represents a local CNS diabetes with mitochondriopathy and failed constitutive mitochondrial peptide elaboration. Support of this model is amassing rapidly. I predict CohBar is on track to have a serious remedy for AD more so than any company in biotech, and this is based on non-privileged information albeit info the company has yet to present in a wide manner.
Above all else I certainly wish Michael Bigger good fortune in his investing pursuits and respect his considerable intelligence. I think it’s fair to assert here that Bigger may be aware of information that is not public and that being a sizable shareholder may have given him access, via an NDA, to data we cannot know that supported his decision to invest. And if so, I hope he wins and wins massively. His integrity, good attitude and kindness are unsurpassed and his cerebral horsepower formidable.