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Thankyou, KT. I can tell he put a lot of effort in that blog and I hope he starts posting here again. His perspective is appreciated.
D
Does anyone know if JBM's anti-ps blog will be available anymore?
The question is: How much?
Benhur Lee, inventor of Lj001, was asked how this antibody compares with other broad spectrum anti-virals (specifically anti-ps). Dr. Lee replied:
Re: Could we possibily have another "Holy Grail" in the making?
« Reply #8 on: February 04, 2010, 02:15:57 am »
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Hey guys,
So I corresponded with Dr. Benhur Lee, lead UCLA researcher of this project, and asked him some questions about Lj001. He was generous enough to reply, and he gave me some more expanded information on this. He also gave me permission to share with everyone here what he replied to me. His only request (as seen in his reply) is that no part of his response is taken out of context. That's why rather than paraphrase his reply I'll just copy it to keep it accurate. The parts in italics were the questions I posed to him in my original email:
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Dear J.
Thank you for your interest. I am pleasantly surprised to see how much attention/discussion it has engendered in forums.poz.com. Clearly, there are informed readers that have asked very germane questions.
Let me try and answer your questions the best I can . . . but I apologize for being a bit nebulous because we have since found out the exact mechanism (which is entirely novel and unexpected) but the patent on this mechanistic discovery has not been filed so I have been advised not to talk specifically about it in public.
(1) what effect can this compound have on HIV-infected cells? What is your hypothesis regarding any benefit to those already infected with the virus, as opposed to the prevention of initial infection?
The compound binds specifically [to] lipid membranes, both cellular and viral membranes. All I can say now is the compound needs to be "activated" in order to effectuate its damaging effects on membrane components (such as phospholipids and cholesterol). The damage is not specific to viral membranes per se (like HIV's) but the reason why it is antiviral at the concentration used is that any damage it does to metabolically active cellular membranes can be repaired by the cell's biogenic repair machinery whereas viral membranes are static and cannot recover from the damage.
That being said, since we know now how to activate the compound (I wish I can be more specific, but I hope you understand the restrictions I am under) we are currently working on strategies to specifically target the activation of the compound on viruses or on virally infected cells. Your question of whether we can specifically target and destroy virally infected cells is something we are exploring by targeted activation of the compound.
(2) Do you know if LJ001 also interacts with aminophospholipid, and could cause the destruction of the infected cell?
No, it does not target a specific aminophospholipid or externalized PS on infected cells as suggested by some of the other bloggers. It does target other features of specific phospholipids and most likely, membrane cholesterol as well. Injection of the compound into mice once a day for 7 days resulted in no toxicity monitored by complete chemistry panels and CBC EXCEPT for a slight elevantion in trigylcerides and cholesterol (also consistent with its lipid targeting mechanism).
In summary, we are working hard on getting out the next paper on our second generation compounds where we could better explain its molecular mechanism of action. Unfortunately, science does not progress as fast as we want to . . . it took us 4 years just to get to this point from our initial discovery of the compound--it is difficult to convince scientists when you propose a paradigm shift of how an antiviral should work.
You may feel free to post some or all of my comments on the forum, please just don't take any of my comments out of context.
Best regards,
Thanks entdoc !
CROI 2010 ----- Interesting Symposium -Targeting the membrane
http://www.retroconference.org/2010/sessions/019.htm
Anyone with access?
Don't know if this has been posted before, however, this article gives a pretty good overview of anti-ps clinical benefits. Haynes mentioned.
"The current paradigm of aPL holds that they are important in thrombosis, but they may have much wider clinical significance"
http://www.medscape.com/viewarticle/587338
I believe they are. IAVI spearheaded that research. CHAVI,who incorporated Dr.Thope's lab and anti-ps research in their quest for a vaccine, joined with IAVI to collaborate on HIV vaccine research back in 2008. See:
http://www.medicalnewstoday.com/articles/104371.php
Volgoat,
I caught that also. Look at the target gp120 that these new bNABS must hit. Bavi could attach to the flipped ps targeting the virus and bring along PG9 and PG16 to do the kill.
I hope they release pre-clinical data soon.
azure,
The sentence that I find intriguing in your link was:
"The antibodies themselves can’t simply be put in a vaccine to immunize people against HIV, said Wayne Koff, senior vice president of research and development at the Vaccine Initiative in New York. While such an effort could have a short-term benefit, a successful vaccine will teach people’s immune systems to produce their own powerful antibodies"
Hope they mean Bavi.
" The work goes on!"
http://www.sciencedaily.com/releases/2009/09/090901143319.htm
The study:
http://www.ncbi.nlm.nih.gov/pubmed/19710597?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Related article:
http://www.ncbi.nlm.nih.gov/pubmed/19640992?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=1&log$=relatedarticles&logdbfrom=pubmed
Hope to see the Duke paper soon.
Some history on Dr. Chabner:
http://history.nih.gov/NIHInOwnWords/docs/chabner1_01.html
It's also on the CHAVI sight:
https://chavi.org/modules/chavi_pubs/index.php?id=1
Does anyone have a subscription to the Journal of Virology?
This could be IT!
http://www.ncbi.nlm.nih.gov/pubmed/19439471?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
CHAVI gives update:
https://chavi.org/modules/chavi_reports/index.php?id=30
Found this interesting ---- antibodies being used by CHAVI:
http://www.hiv.lanl.gov/content/nab-reference-strains/html/home.htm
I wonder if he tried any of pphm's meds.
It seems the word is spreading.
http://forums.poz.com/index.php?topic=22113.0
I believe the adaptive immunity component is the pphm connection.
Don't know if the following has been posted earlier, but interesting--
http://jac.oxfordjournals.org/cgi/content/full/54/5/915
Of the more than 20 drugs used for HIV therapy, all have AEs (adverse effects). Some more than others. These AEs can range from mild upset stomach to cancer. However,a patient must take more than one drug to hit the virus at different locations to maintain undetectable viral load in the blood. For most patients 3 or 4 drugs are needed (a heavy burden. Also, the virus is able to mutate and render these drugs much less effective or useless to the patient over time so the drug regimin must be changed.
Should BAVI be effective (I believe it will),the virus cannot
mutate against it since it goes after a primary function of the cell (exposed ps) so even if BAVI doesn't CURE HIV it could be used as a therapy indefinitely. And its top line safety data is also encouraging.
Jake,
Under Fig 14 of the patent (tavicin is mentioned as anti-ps).
THANKYOU JAZZ!!!!!
How many doses of a multicomponent HIV-HTV-I vaccine can 50 billion dollars buy?
Jazz,
Your research ability is only surpassed by your humanity and it comes through with your posts. Chavi would not say or do anything until they have dotted every i and crossed every t.
I believe they have "THE HOLY GRAIL". Thankyou
Jazz, one of the many insidious pathogens of the HIV virus is its ability to hide in resting cd4 cells (latent virus)as I'm sure you are aware of. All the medications out today are only able to clear the free flowing virus in the blood. This can only be done until the virus changes its protein coat rendering the drugs ineffective (mutations).The beauty of anti-ps is that ps is exposed on both the virus and those latent infected cd4 cells thus the virus can't mutate against bavi. The virus would have to evolve. Anyone who has been following Dr. Thorpe's research can understand how important this mechanism is not only with respect to HIV but to other virus and also cancer. Combine the former moa with top-line safety data as seen in the clinical trials to date the mind is boggled. I pray this is fast tracked.
JBM,I have been following Dr. Thorpe's research for the last 8 years and I have been reading your posts for about the same length of time. I want to say thankyou for all you do in my first post on IHUB. The validation of the science is certainly exciting especially for those who have loved ones waiting for something as exciting as anti-ps therapy. I am also aninvestor in PPHM for 7 years. I am also anxiously waiting for the CHAVI papers and in particular the results of CHAVI 006! I don't think it will be too long now! Thankyou again,
D