- AER002 is probably the two mAbs P2G3 LS & P5C3 LS derived from a human, which the inventors of Aerium Therapeutics describe in their paper: ncbi.nlm.nih.gov/pmc/articles/P…
- It has strong neutralization against all SARS-CoV-2 tested (up to BA.5) ➡️ matches the persistent viral stains
Both mAbs have Antibody-Dependent Cellular Cytotoxicity (ADCC) & AD Cellu Phagocytosis (ADCP):
mAbs bind to the spikes that are left on the surface of the infected cells and their Fc regions (their tails) act as receptors for NK cells & phagocytes to kill & eat infected cells.
That is: they can completely clear out a viral infection, even if there is no detectable viral replication. This circumvents SARS-CoV-2's immune evasion.
PwLC were found to have impaired Antibody-dependent NK cell activation, but not ADCP. medrxiv.org/content/10.110…
The antibodies contain the LS mutation in the Fc region, which appears to confer a half-life on the order of months.
So there's a scenario where it helps to suppress but not fully clear the infection, where you get an infusion 2 or 3 times a year.
The two mAbs given together would also increase the threshold for the virus to develop resistance.
The authors state that the antibodies have good effectiveness against mutations that would escape one or the other.
Downsides:
➡️ Needs IV
➡️ Anecdotally, mAbs sometimes cause inflammation, especially with ADCC. This needs to be managed clinically to prevent collateral damage but not stop the immune system working.
➡️ Can't reach the brain
➡️ If neurons are infected, maar nog want to kill them
They are trialing it in 20 people, with 10 controls with what seems like a pretty high dose (1200mg)
Most other mAbs have very limited ADCC, except for Sotrovimab
If you want to get better at evaluating science, I can highly recommend the book Science Fictions by @StuartJRitchie
I just finished it, and it has really emphasized the many issues with science & I learned a lot!
A few takeaways 🧵
The image above illustrates it well: looking only at registered trials & their primary outcomes, only 50% of trials found a positive effect of various depression treatments.
However, through publ. bias, outcome switching, spinning results etc, the literature looks much rosier!
Treat every paper with the scepticism for a “CBT for ME/CFS” paper
Just because you like positive results, doesn't mean they're well-supported
Sample: they focused on the most severe patients, who had at least some measurable biological dysfunctions (POTS, microvascular, endothelial, pulmonary)
I really like this: presumably easier to find abnormalities in extreme population
Severity doesn't seem measured via scale 🫤
Increased IgG to SARS-CoV-2 in Long Covid vs. convalescent
Results
" In 64 SSRI users, median concentrations of plasma-free and platelet serotonin were 10-fold and 14-fold lower, respectively, than in 64 matched controls." journals.sagepub.com/doi/10.1177/00…
Study 2)
"There was a significant decrease in 5-HT levels over treatment in all MDD subjects (t = 6.2, p = 0.000003). The decrease was significantly more prominent in responders compared to non-responders (t = 2.1, p = 0.047)." pubmed.ncbi.nlm.nih.gov/30831543/