Dr. KSS of BioPub's response to discussion below..he thought I had the thoughts about Rantes, but I don't have a clue about it..I think a subscription to BIOPUB is very worthwhile especially if you follow the Bios
Covid immunogical phase is being mediated by rantes and other cytokines leading to ards not fibrosis. Nmda inhibition may help ipf by inhibiting fibrosis production and chonic cough by inhibiting fibrosis and inhibiting cough reflex with its nmda action on nerves
Lowersioux5 Sunday, 08/16/20 12:50:20 AM
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Why do you say NMDA inhibitor only helps against fibrosis?
Have you looked at the UT study linking Ifenprodil to potential COVID-19 treatment?
NMDA receptors are linked to glutamate and cytokine release, correct?
Immune based signal, not neuronal. Upregulation of NMDA receptors in severe COVID-19 patients means Ifenprodil could disrupt NMDA receptor signaling.
In my completely ignorant opinion, anyways.
Hi Jamie:
Thanks for writing.
Our original entry into Algernon was, yes, for the IPF story, in addition to the GIRK receptor antagonist story and to quite stark mucosal abatement of activity in animal models of IBD all mediated by ifenprodil. Moreover, ifenprodil is highly antitussive in animal models, and does not appear to act via the same receptor pathway chased by Bellus.
As I have disclosed previously I am a consultant to Algernon and was very much on board with the internal decision to pursue Covid-19. I would note that the FDA enthused to an exceptional degree about the firm's Covid-19 trial plans and proposed MOA, and that pulmonology KOLs have signed on left and right. The FDA greenlighted the trial in record short time and even authorized the firm to use overseas supplies (Japanese and Korean) of ifenprodil because at that juncture, manufacturing of cGMP drug lagged. This is a highly unusual move for the FDA, and smacks of aligned thinking by the agency and encouragement by the agency for the firm to proceed, the motif being that Covid-19 drives pulmonary fibrosis. The agency has not modified its stance on Algernon's trial plans and indeed Covid-19 ifenprodil trials are going on at US centers.
Regarding your RANTES contention and assertion that fibrosis is not the issue, I would gently assert the non-consensus on that and vigorous debate, and the observation of numerous Covid-19 clinical phenotypic behaviors, for lack of a better term, some of them blending and overlapping. I think you would concede that ARDS is not an indication for lung transplantation and that pulmonary fibrosis is, and that several patients are now s/p lung transplant for Covid-19. A very close friend is a British intensivist who has routinely bronched and done biopsies on these patients, and she describes the fibrosis as histopathologically "wicked."
Pulmonologist Martin Kolb, MD, Professor and director of pulmonary services at McMaster University, will be our guest for one of the Algernon upcoming webcasts, and you are welcome to put your views to him, but I think you will find him, like me, not sharing your view.....though both of us lack the ferocity of the ideologue. It's simply what's being described, and has considerable analogies to end stage pulmonary complications of influenza. Kolb endorses the Algernon approach, and was eager to do so at the outset.
While blind is unlikely to be broken early on the Covid studies by Algernon, I still would not exclude the possibility of some interim data by the time of the webcasts given the unusual speed of enrollment of study patients at a Romanian large trial site. Bear in mind that in H5N1 animal models where subjects die of pulmonary fibrosis, ifenprodil therapy rescues close to half of infected animals from death, a sobering observation.
I would kindly assert the jury remains out on the pulmonary drama of Covid, a fact not wasted on Altum/BetterLife, where I am a board member and also have guided clinical trial plans in Covid. It may be that what you contend is correct some of the time, but not universally. You didn't specify whether you are leading clinical trials but the unfortunate fact is the bete noire of all experience is that it boils down to anecdote if not in the setting of clinical trial. Last time I checked, the plural of anecdote is not "data."
I hope you will join us for the webcasts and participate and have dialogue with Dr. Kolb and air your views, as plurality and dissension are welcome. If you can't attend live, I am happy to put questions to Dr. Kolb on your behalf if submitted in advance.
Bottom line: An Algernon investment is not a pure Covid play. It is an ifenprodil versatility play. We believe the company has done right by shareholders by immersing itself in the Covid fray because of a genuine consensus among company advisors, consultants and insiders the agent has a meaningful chance of helping, and certainly will not harm patients. Being of value to mankind's health is Algernon's sole goal, because appropriate and justifiable lucre accrue to those companies whose agents make a difference. The company's Covid 19 pursuit is neither gratuitous nor opportunistic nor craven, but driven by among the purest corporate motivations I've ever witnessed. Covid 19 may well no longer be a problem in a year, which could leave the company's efforts in the space bereft of financial payback. It's a chance they're willing to take on a shoestring budget because those of us with the company believe an enormous opportunity is at hand to do something good. Meanwhile, I'd note by the by that the approved agents for IPF are in Covid 19 trials. Ergo, clearly I'm not the only one who regards fibrosis as a major driver of outcome here.
Appreciate you writing. Try to join us for the webcasts.
Best,
KSS
AI
