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Vittoz quotes correctly my interview broadcasted some time ago by Ici et Maintenant. Indeed, back in the nineties, my team (I was then research director with the French National Center for Scientific Research, CNRS) investigated the precise mechanism responsible for the high mutation rate of HIV reverse transcription, which is at the root of the deadly viral strategy. As a result, we could establish detailed nucleotide characteristics either enhancing, or reducing the mutation rate. From a therapeutic point of view, increasing the mutation rate will abolish viral infectivity (equivalent to “viral decay accelerator” advocated by Koronis), whilst decreasing this rate will stabilize the virus, thereby allowing the immune system to clear the viral load, just as it does when facing conventional microbial pathogens (immunization against the stabilized HIV strain). Based on the criteria enabling nucleotide analogs to force the virus into one of these “viral suicide” pathways, we found many such analogs in a class of natural nucleic acids present in the biomass, in particular transfer RNAs. We further selected those analogs able to dock into the viral RT, but unable to fit into the cellular, nucleic acid synthesizing enzymes, thereby precluding any genotoxicity of the drug, in particular for mitochondria (for details, see www.vigilentech.com). My employer filed (1999) a patent on this new therapeutic approach (granted by USPO in 2004), but refused to support preclinical studies. I left CNRS and founded a start-up, trying to rise the funding needed for the study ($500k). The many applications I filed with French government agencies (including ANRS, the National Agency for AIDS Research) were systematically rejected. Comments invariably alleged that support was spent for “projects of higher priority”, none even considered or commented the scientific or medical merits of the project, which had of course been carefully considered by CNRS before filing the patent. Someday a member of a board of one of these agencies, who had ties with the pharma industry, told me frankly, of course without a witness, the obvious reason of the systematic rebuttal, as quoted by Vittoz. Understandably then, I watched closely the trials undertaken by Koronis. I was surprised by the failure (revealed by Paul Dalton in ProjectInform) of KP 1461 to reproduce results published earlier, in particular by Karen Anderson’s group of Yale in 2005 dealing with the active moiety of the prodrug, KP 1212. I sent Lawrence Loeb, scientific adviser to Koronis who contributed to the development of the vda concept, a mail in July suggesting possible reasons for the failure. The “passage” test involves two actors mainly: MT-2 cells which had been used for the earlier passage experiment, and KP 1461. May be the MT-2 batch used lostmeanwhile its ability to convert prodrug KP 1461 to KP 1212, or that the KP 1461 tested now is inactive, for instance due to tiny steric differences (depending on the synthesis method) with the earlier version? Loeb did not respond so far. Accordingly, I believe there is only a technical problem which Koronis could rapidly settle.
To JF Vittoz ????...????? Would be so kind to post some more information?
I agree with the opinion posted aug. 6 by Veryfishy. Actually, an approach (dubbed « viral suicide »), similar in part to the VDA has been advocated by a renowned senior french scientist named Claude Reiss. In an interview broadcasted by a french radio station (« ici et maintenant »), he explained that he has a list of some 100 modified nucleotides of natural origine, allowing to take control over the viral mutation rate, either ridding the virus with errors as vda and kp 1461 does, or cancelling mutations, thereby allowing the immune system to get hold of the stabilized virus. He also complained that he was bluntly barred from getting support for preclinical trials from the french National Agency for AIDS Research and said that he was told by people from the pharma industry that he « would not be allowed to ruin a $36 billion/year (AIDS) business », as this new therapy would likely achieve full viral clearance.
As an HIV + patient and so young at that it seems to me through my research, that there has always been known cures but are unusable on humans due to Toxicity levels. On the other hand why continue this painful cycle of "Oh we may have found a cure" giving us false hope only to have it crushed. There is a strong need for researchers to honestly come together in one location and work together on finding a cure!
Kp-1461 trial has not been a failure but only suspended, please wait a while, Koronispharma team is planning to go ahead with upcoming humans trial. Give them the time to adjust the chemical formulation and do not worry about Becker's resignation. It is not true that all the patients had no clinical benefit from kp-1461, few had hiv control replication and few is not like none. Probably the long lasting viral reservoirs need a longer trial. Please read - KP-1461 redux -
There's something very weird going on here. It doesn't make any sense that the drug showed so much promise before invitro and they went ahead to phase 2. Then when they went back to repeat the experiment, it has no affect at all. Seriously... are we supposed to believe this? The FDA is probably in bed with companies that manufacture HIV drugs that just suppress the virus, and they know if kp-1461 did eradicate the virus, their fat bankrolls would start getting smaller. This may sound like a conspiracy theory, but what am I suppossed to think? This isn't ok, and someone need's to provide some answers to the public who's been eagerly awaiting some promising results about this drug.
Thanks a lot Paul It seems, hopefully, that kp-1461 is not completely gone, anyway until official info from Koronispharma it's better to cross the fingers again.
Johnny1
What you said is terrible.... - immunization against the stabilized HIV strain - , Does it mean that the immune system could clear the remaing hiv or destroy latent hiv reservoirs ? Now i understand why they have been coerced to stop the trial in that way....THE BIG PHARMA WANT TO MAKE MONEY WITH THE CONVENTIONAL DRUGS AND THEN, AFTER YEARS, TO FIND (or let others to find it ) A CURE, MAKING FURTHER MONEY. Anyway BIG PHARMA AND FDA go to sleep together, there are no doubts.
October 3, 2008