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Prana Biotechnology Limited Message Board

kadaicher1 138 posts  |  Last Activity: 6 hours ago Member since: Jan 23, 2004
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  • Reply to

    Tau

    by kadaicher1 Dec 19, 2014 10:13 AM
    kadaicher1 kadaicher1 6 hours ago Flag

    ITM, as I understand it GSK modulation is happening continuously through competing modulators. GSK dependent tau phosphorylation is happening all the time as microtubulins are deconstructed and reconstructed. One of the competing compounds for GSK modulation is insulin, zinc is another and there are others. One effect of PBT2 is that it corrects any zinc imbalance(shortage), when free matals are available. When GSK is not under control hyperphosphorylation is possible. PBT2 just restores the normal metal levels used in this natural process. Lindquist hinted that MPACs may have more benefit from how they move metals around inside the cell, rather than metals taken from outside the cell.
    PBT2 can prevent the hell out of tau and Ab formation in the model, but now the technology exists, it would be great to see the results in a clinical trial.
    All the above is just an opinion formed from papers I have seen, so don't hesitate to correct anything you see is wrong.

    Sentiment: Strong Buy

  • Reply to

    Tau

    by kadaicher1 Dec 19, 2014 10:13 AM
    kadaicher1 kadaicher1 18 hours ago Flag

    ITM, Prana long ago demonstrated that by an indirect metal dependent modulation of GSK 3 PBT2 could prevent hyperphosphorylation of the microtubulins that form the tau tangles. They have also demonstrated in the animal model PBT2 can remove the tau tangles from the neurons in the model.
    They have also demonstrated clearance of HTT in the Huntington's model. All are metal dependent processes.
    I personally can't see secretes modulators working. Reason, secretase modulated APP production is a reaction to a sick cell condition. As the cell is dying trophic factor is cut off, APP goes into a secretase modulated hyper expulsion of amyloid from the cell before triggering the death receptor. I don't see good from keeping that cell on life support by shutting down or reducing secretase. Also Tanzi himself with Moir demonstrated amyloid to be a powerful antimicrobial peptide. If the brain is under a pathogen attack and one of its guns is kept at bay by secretase modulation I can see that not ending well. Amyloid bunches around brain injuries.
    The Chinese have done some research on a gerbil AD model and as cells were cleansed, the secretase levels naturally backed off.
    No argument that MACs can get into the metal imbalances and correct the condition before AD starts, but the best results so far have been on the more advanced patients. So it can work at various stages of the disease. Tau is just one of its many functions, and the prevention of tau tangles by modulation of GKK3 is at the very start of the process, and is just one of the arms of the MPAC MOA.
    What I would most like to stress is that the PBT2 MOA is nothing like Gante.

    Sentiment: Strong Buy

  • Reply to

    Tau

    by kadaicher1 Dec 19, 2014 10:13 AM
    kadaicher1 kadaicher1 Dec 20, 2014 7:33 AM Flag

    When you think about, the IMAGINE trial and the extension trial will be the first two tangle reducing drugs to report. Unfortunately the tau levels are not being monitored by either Prana or I even the LMTX trials being run by TauRx. The technology to do that did not exist at the start of the IMAGINE trial.
    Right now I am interested in the ability of PBT2 to remove Tau in relation to the Huntingtin protein build inside HD neurons, and hoping the technology used to image Tau can also be used to monitor the HTT build inside HD effected neurons. That is most likely to be the first trial off the rank.

    Sentiment: Strong Buy

  • Reply to

    Tau

    by kadaicher1 Dec 19, 2014 10:13 AM
    kadaicher1 kadaicher1 Dec 19, 2014 5:52 PM Flag

    Always have been. I just thought that point needs emphasis today. Also remember Roche have just terminated the Gante prodromal trial, not the mild Alzheimer's trial for the drug.

    "Summary of new data presented at the 11th International Conference on Alzheimer’s and Parkinson’s Disease

    Melbourne – 8th March, 2013 Prana Biotechnology (NASDAQ:PRAN; ASX:PBT). Following on from the announcement released on 4th March, 2013 and at the request of the Australian Securities Exchange, the company is pleased to provide further detail in respect to the presentation of the new data demonstrating the ability of PBT2 to reduce the damage to brain cells, caused by the accumulation of the tau protein and preventing subsequent cognitive impairment.

    The data was generated in an animal model that over produces the tau protein giving rise to ‘tangle like’ inclusions similar to those which cause neuronal death in Alzheimer’s disease (AD). Importantly, whilst the anti-aggregation effects of PBT2 on Abeta have been well documented1, these results were generated in a model which is independent of the presence of Abeta, indicating that PBT2 has the ability to prevent neuronal damage via multiple metal mediated pathways, including Abeta and tau aggregation."

    Sentiment: Strong Buy

  • kadaicher1 kadaicher1 Dec 19, 2014 11:50 AM Flag

    They may also be waiting on the results of the IMAGINE extension trial.

    Sentiment: Strong Buy

  • Reply to

    Science losing steam!

    by bgfalter Dec 19, 2014 9:50 AM
    kadaicher1 kadaicher1 Dec 19, 2014 10:27 AM Flag

    Prana is now in a much stronger position. We know it removes plaques, studies have shown it removes tau tangles in cells, and the metal chaperon process it accomplishes that with has multiple beneficial effects inside neurons.
    Gante is like Bapi on steroids, and now we know it does not even work in prodromal patients. Maybe removing the plaques and the metals they hold is just not the way.
    MPACs are completely different MOA.

    Sentiment: Strong Buy

  • kadaicher1 by kadaicher1 Dec 19, 2014 10:13 AM Flag

    Prana's PBT2 differs from Gante in a few very important ways. It has been shown in preclinicals to also remove the tau tangles inside cells. When IMAGINE extension reports two year data, it needs to be remembered this is also a tau drug. Unfortunately when IMAGINE commenced, there was no way to observe tau removal in the living brain, although the imaging technology now exists.
    Gante, the amyloid buster failed, maybe a slow and gentle treatment with several arms to its MOA will prove more appropriate to treat a disease which has taken 80 years to build. Maybe it will take a combination.

    Sentiment: Strong Buy

  • kadaicher1 kadaicher1 Dec 19, 2014 9:50 AM Flag

    Another tragedy. I get the feeling Roche in their rush really rolled the dice on this. After a tiny phase 1, They started the phase2, then converted that into a phase3. That MAB was the strongest amyloid removal product so far. They still have crenezumab, selected for the Columbian trial before the phase 2 was complete, which failed. The crenezumab trial did demonstrate a few trends.
    Suddenly the IMAGINE extension trial results assume more importance.

    Sentiment: Strong Buy

  • Reply to

    The HD prion?

    by kadaicher1 Dec 16, 2014 2:04 PM
    kadaicher1 kadaicher1 Dec 18, 2014 6:12 PM Flag

    There is a something be said for Prana's debt free development style. DNDN has a successful $300m drug to market, but cannot service the huge debt for long enough to reach break even point.
    "NEW YORK, NY / ACCESSWIRE / December 1, 2014 / With the recent bankruptcy of Dendreon Corporation (NASDAQ:DNDN) due to disappointing sales of its flagship Provenge prostate cancer vaccine, the future of cancer immunotherapy just got a bit cloudier. While Provenge itself will survive, Dendreon may end up going private in a debt restructuring deal.

    But while it may look grim now, the fact remains that sales of Provenge will reach the $300M mark this year, a nice sum for any company from startup biotech to Big Pharma. It just wasn't enough to overcome the debt incurred to develop it. Clearly then, there is a significant market for cancer vaccines. The trick is to develop the treatments at much cheaper cost."

    Sentiment: Strong Buy

  • Reply to

    The HD prion?

    by kadaicher1 Dec 16, 2014 2:04 PM
    kadaicher1 kadaicher1 Dec 18, 2014 3:50 PM Flag

    HD could take them to a higher SP and improve raising capabilities for the multiple trials they need to be running.

    Sentiment: Strong Buy

  • Reply to

    Science Matters Here

    by tb00tb00a Oct 9, 2014 10:22 AM
    kadaicher1 kadaicher1 Dec 18, 2014 3:27 PM Flag

    I guess he is talking about metal dishomeostasis. Here posted on the NIH site "Challenges Associated with Metal Chelation Therapy in Alzheimer's Disease" Talks about Metal targeted therapies. They seem to know about it.

    NAS seem to know about it
    "Prana Biotech Alzheimer approach supported by study
    Mar 6 2014, 10:49 ET | About: Prana Biotechnology Ltd (PRAN) | By: Douglas W. House, SA News Editor Contact this editor with comments or a news tip
    The therapeutic rationale of Prana Biotechnology's (PRAN) PBT2 Metal-Protein Attenuating Compound ((MPAC)) gets a boost from a just-published study by the journal of the National Academy of Sciences USA."

    The Whitehead institute did a study on around 200,000 compounds and found MPACs emerge at the top. They wrote a paper on it but what would they know. Who the hell is Susan Lindquist compared to Biotech Invest.

    Sentiment: Strong Buy

  • kadaicher1 kadaicher1 Dec 18, 2014 1:28 PM Flag

    It looks like it is an imorovement over the current Chorea drug generics.
    "Tetrabenazine, marketed as Xenazine in the United States, is expected to lose its market exclusivity for treatment of Chorea in August 2015. If approved, SD-809 may compete with generic versions of the drug.

    "Given the well-known side effects of tetrabenazine, which holds a black box warning for suicidality and depression ... we expect SD-809 to gain significant share over generics if approved," William Blair analyst Tim Lugo said.

    The drug's safety profile was better than expected and it also met several secondary goals which should significantly differentiate it over tetrabenazine, he added."
    I guess that is a good reason for the $1B+ market cap. PBT2 has a wider target and with other indications and suggested off label use, Prana's cap could be driven much higher. Nice to see it done here on just one side of HD

    Sentiment: Strong Buy

  • Reply to

    What a fiasco!

    by bgfalter Dec 18, 2014 11:12 AM
    kadaicher1 kadaicher1 Dec 18, 2014 12:17 PM Flag

    I think you could be correct rkf. Dec1 SP $ $1.57 and falling. He said:
    "No matter what happens never question a Pran Nerd about their lofty and brainiac Posts. It is the blind allegiance to their dogma that will Rule the Day. Never call them into question over Old Posts that resurface daily....this is the Holy Graille to them...lol
    and
    "But Oh yes that will carry the day. Pass around the Petri dish for today's offering as you go broke. God these people make me sick."
    There goes a 30% profit for anybody who listened to him that day. Well Done Chatterly.
    He does not seem to understand that this is a science based stock, and science matters in where this goes from here. I think at this stage it is also good to keep an eye on technical indicators, but he does not even mention them. Maybe you are right, just a troll.

    Sentiment: Strong Buy

  • Reply to

    What a fiasco!

    by bgfalter Dec 18, 2014 11:12 AM
    kadaicher1 kadaicher1 Dec 18, 2014 11:49 AM Flag

    That was good advice then, but not at these levels. Can't you see he difference?

    Sentiment: Strong Buy

  • kadaicher1 kadaicher1 Dec 18, 2014 11:30 AM Flag

    I am not sure what stage they are at with the brain cancer drug, but it is also going through tox studies and will be ready for the clinic at some time yet to be forecast.

    Sentiment: Strong Buy

  • I am sure not selling any. AD results, followed by a pivotal HD trial startup, followed by the PD drug entering the clinic in any order you like. It is all positive.

    Sentiment: Strong Buy

  • Reply to

    What a fiasco!

    by bgfalter Dec 18, 2014 11:12 AM
    kadaicher1 kadaicher1 Dec 18, 2014 11:15 AM Flag

    Yea, like the last time it increased about 1000%. There were turkeys giving the same advice back then to sell low. Brilliant strategy. Thanks for the advice.

    Sentiment: Strong Buy

  • Reply to

    The HD prion?

    by kadaicher1 Dec 16, 2014 2:04 PM
    kadaicher1 kadaicher1 Dec 18, 2014 11:12 AM Flag

    I wish the FDA was wired that way ITM. If I recall the trends identified by Masters in the 1 year results, apart from hippocampus volume, were very
    different in the treatment arm compared to the placebo. That is another thing to check in the placebo crossovers as proof of disease modification, along with the brain volume changes seen in the topline 1 year results. I am not saying we will see those changes, but it has to be a very good possibility.
    If they see enough to justify a phase3 I am pretty sure it will boost the price some. Now they have tested PBT2 from moderate to prodromal, so they should have the data they need. If you count the CQ trial, Prana have even tested MPACs in advanced stage disease.

    Sentiment: Strong Buy

  • Reply to

    90% of the posts on this board come from ITM andRKF!

    by bgfalter Dec 18, 2014 10:00 AM
    kadaicher1 kadaicher1 Dec 18, 2014 10:41 AM Flag

    There is a lot of scientific info posted here, none by you. Nobody needs you to advise on who to ignore.

    Sentiment: Strong Buy

  • kadaicher1 kadaicher1 Dec 18, 2014 6:47 AM Flag

    I guess Dr Shoulson does. Do you understand the difference between a phase2 trial looking for ways to design a phase 3 trial and an actual phase 3 trial.
    They have another chorea drug to compete with and yet a $1.3B market cap.
    Do they have other products?

    Sentiment: Strong Buy

PRAN
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