An email I sent to Dr. Pourhassan - A way to im
Post# of 148172
A way to improve the efficacy of leronlimab in PREP
After doing some reading of medical texts I may have spotted a way to increase the effectiveness of leronlimab in PREP. It might also help in reducing the amount of 10 week virologic failure in regular HIV treatment.
Basically, blocking galectin 3 should reduce vaginal transmission of the HIV virus by reducing the ability of the virus to adhese to dendritic cells. It also may help knock down the ability of HIV to launch from follicular dendritic cells, reducing the burden on CCR5 receptors.
There is also the possibility that galectin 3 blocking and leronlimab may have a symbiotic effect in cancers and inflammatory diseases.
Right now there is a galectin 3 blocker called GR-MD-02 from Galectin Therapeutics that like our drug has no SAEs and would work ideally.
I hope you can have your scientists look at the potential benefits of the combination of drugs and if it looks promising pass it along to the Red Cross PREP team in Thailand.
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Furthermore, we studied DC exosome mediated HIV-1 transmission to T cells in the presence of various concentrations (0–100 mM) of β-lactose, a natural antagonist of galactin-348,49, and observed that β-lactose significantly blocked virus transmission (Fig. 4E). These results indicate that fibronectin and galectin-3 may be involved in HIV-1 transmission mediated by exosomes derived from HIV-1 infected DCs.
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Previous studies have shown that fibronectin and galectin-3 can enhance HIV-1 entry and infection up to 20 fold.
https://www.nature.com/articles/s41598-017-14817-8
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Dendritic cells are crucial in the dissemination of HIV-1 following primary infection as experimental results have suggested that they might be the first cell type to be infected after intravaginal inoculation.
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Recent results have suggested that infection of DCs is required for transfer of the virus to CD4+ T cells and this capability is maintained for periods of time greater than 3 days.
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Follicular dendritic cells are capable of capturing antigen and preserving it on their cell surface in its natural conformation for extended periods of time, similarly they are able to trap HIV-1 and become a reservoir for the virus, although they are not productively infected.
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Importantly, it has been shown that FDCs can convert HIV-1 from a neutralized form into an infectious form even in the presence of excess of neutralizing antibody.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683678/