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Waking up dormant cells

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John2038:
Sources
theaustralian.com.au
radioaustralia.net.au
..
By using cancer drug, Vorinostat, for two weeks, Prof Lewin had been able to turn on sleeping HIV-infected cells so they could be detected

Dr.Strangelove:
Lewin also gave a talk at CROI

It's good to see a step in the right direction to tackle the dormant cells. But it seems that HIV lies dormant in different types of cells, not all of them can be awaken by Vorinostat. So, this is only a piece of the puzzle. Like always.

geobee:
Not to mention it's carcinogenic. 

A lot of work is being done to wake up latent cells.  Google "Bryologs" for example (and there's a thread here about that somewhere).  Smart people (Drs. Siliciano, Margolis, Deeks, etc. )  I'm confident they'll find something that works and hopefully isn't too toxic.

elf:
Latent reservoirs cleaning ''substances'' need to be tested, and it can take 10 years or more.

So, why not use meds that are considered safe, and are already widely used in clinical settings, like

1) Disulfiram /Antabuse
http://en.wikipedia.org/wiki/Disulfiram



   
--- Quote ---RESULTS:

    DSF reactivated latent HIV-1 expression in the U1 cell line, but not in the J89GFP or ACH2 cell lines. Interestingly, we found that DSF significantly reduced phosphatase and tensin homolog (PTEN) protein levels in U1 cells and in resting CD4 T cells from HIV-negative donors. Decreased PTEN resulted in increased phosphorylation of protein kinase B (Akt) and activation of the Akt signaling pathway. Consistent with these finding, pharmacological inhibitors of Akt and nuclear factor-kappaB (NF-κB) block the latent HIV-1-reactivating activity of DSF. Furthermore, we show that HIV-1 expression in the U1 cell line could be activated by a small molecule inhibitor of PTEN or by siRNA knockdown of PTEN expression. Neither the J89GFP nor ACH2 cells express PTEN, explaining the lack of DSF effect on HIV-1 expression in both these cell lines.
    CONCLUSION: DSF reactivates latent HIV-1 expression via the Akt signaling pathway through depletion of PTEN.
--- End quote ---

http://www.ncbi.nlm.nih.gov/pubmed/22739395


2) Miltefosine / Impavido
http://en.wikipedia.org/wiki/Miltefosine



--- Quote ---    Miltefosine targets HIV infected macrophages, which play a role in vivo as long-lived HIV-1 reservoirs. The HIV protein Tat activates pro-survival PI3K/Akt pathway in primary human macrophages. Miltefosine acts by inhibiting the PI3K/Akt pathway, thus removing the infected macrophages from circulation, without affecting healthy cells.
--- End quote ---

geobee:
Dr. Deeks at UCSF is testing disulfiram / antabuse.

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