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Prana Biotechnology Limited Message Board

kadaicher1 67 posts  |  Last Activity: Nov 25, 2014 3:11 AM Member since: Jan 23, 2004
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  • Reply to

    General Observation

    by goutah3006 Nov 24, 2014 2:30 PM
    kadaicher1 kadaicher1 Nov 25, 2014 3:11 AM Flag

    Improvements in executive function are what attracted HSG to PBT2. Earliest manifestation of HD is deterioration of executive function. TMTB is the principal test for executive function. The results were enough to attract one of the world's foremost HD researchers onto the Prana board.
    So far this is looking good for HD.
    I think maybe you are the scam. I will go with Dr Shoulson's opinion on PBT2 for HD, rather than yours which changes depending on your holding.

    Sentiment: Strong Buy

  • kadaicher1 by kadaicher1 Nov 24, 2014 11:39 AM Flag

    Any good news from the AD, Huntington's or soon to be Parkinsons clinical efforts could see this returning to former highs. Remember those former highs were in anticipation of good AD results. We didn't see the good results because of an underpowered trial which did not disprove anything. Once they start retesting at 2 years which is very soon, anything could happen.

    Sentiment: Strong Buy

  • Reply to

    Another look at IMAGINE Data

    by interestingtome Aug 14, 2014 3:59 PM
    kadaicher1 kadaicher1 Nov 8, 2014 8:03 PM Flag

    Hi Pivalde, I care a lot about the PET results of this particular trial. The reason is that PBT2 does not stick to plaques to remove them. It does nothing to directly remove plaques. All it does is out compete AB plaques for free metals, In doing this the plaques lose the metal attracting them and dissipate. All of which we all know.
    The kicker is that plaque removal is an indication that the metal chaperon process is indeed happening, with all the possible downstream advantages. If it is not reducing plaques, then the whole process of chaperoning metals from the plaques into the neurons is called into question.
    Luckily it was removing plaques.
    ITMs very logical work with those trial graphs and historical trend graphs was a great confidence booster for me.

    Sentiment: Strong Buy

  • Reply to

    1Y RSI now below 30.

    by kadaicher1 Nov 4, 2014 2:02 PM
    kadaicher1 kadaicher1 Nov 6, 2014 5:53 PM Flag

    Yes, and as commented before, the Tanzi lab breakthrough brings testing all those synergies into the realms of possibility.

    Sentiment: Strong Buy

  • kadaicher1 kadaicher1 Nov 6, 2014 3:07 PM Flag

    Proposed minimum price is $5. Sounds like a very strong buy to me. What news is on the way? What have they seen to prepare something like this.

    Sentiment: Strong Buy

  • Reply to

    1Y RSI now below 30.

    by kadaicher1 Nov 4, 2014 2:02 PM
    kadaicher1 kadaicher1 Nov 6, 2014 2:25 PM Flag

    Still below 30 and the s/stochastic has crossed. Signs looking for a recovery.

    Sentiment: Strong Buy

  • Reply to

    1Y RSI now below 30.

    by kadaicher1 Nov 4, 2014 2:02 PM
    kadaicher1 kadaicher1 Nov 5, 2014 8:27 AM Flag

    I would guess 434 will be first news. Last time I asked them about what they had seen in the preclinical testing, they seemed very proud of that Parkinson's/movement disorder candidate.
    I need to get up to speed on the current state of brain cancer research, but last time I checked there was precious little available .If 519 can demonstrate synergy Temodar, as it did in pre clinical models, then I think there is an urgent need for PBT519. The industry is now looking at cocktails and anti angiogenesis drugs like Avastin and Zactima have been used to extend survival up over 3 years.
    Like the angiogenesis blockers PBT519 can probably prove a decent safety profile.
    Last I saw the standard was Radiation with Temodar.

    Sentiment: Strong Buy

  • Reply to

    1Y RSI now below 30.

    by kadaicher1 Nov 4, 2014 2:02 PM
    kadaicher1 kadaicher1 Nov 4, 2014 11:02 PM Flag

    Whatever way you look at it we should have a pivotal phase 3 trial for HD approval very soon. When asked why he joined the Prana board, Dr Shoulson reply included " As recently reported, Reach2HD showed safety and tolerability and signals cognitive benefit that may prove to be reproducible and clinically meaningful."
    "I accepted the position as non-executive director in order to provide clinical research expertise and help ensure PBT2 was developed to its full potential in HD."
    I am not sure any other drugs can claim signals of cognitive benefit in a disease modifying HD drug. Those quotes were from "HD insights Vol 9"

    Sentiment: Strong Buy

  • kadaicher1 by kadaicher1 Nov 4, 2014 2:02 PM Flag

    Bands are tight, it will not take much to make this pop. Way too cheap right now.

    Sentiment: Strong Buy

  • kadaicher1 kadaicher1 Nov 2, 2014 2:57 AM Flag

    Thanks for posting. I also hope Prana are up to speed with this, and agree that Prana could not have anyone better than Ira Shoulson to lead Prana into any FDA meetings on this subject.

    Sentiment: Strong Buy

  • Reply to

    The forgotten trial

    by kadaicher1 Oct 30, 2014 2:49 PM
    kadaicher1 kadaicher1 Nov 1, 2014 3:36 PM Flag

    I am sure they have a truckload of AD data over more than a decade of development. Now we need that two year safety data. There is probably enough to make docs interested on off label AD use, for sure for 6 months. The effect on brain shrinkage in both AD and HD is great, but for me the question is "did the Reach2HD trial provide enough data for Prana to design a quick pivotal trial for approval in HD."
    It is still the fastest way to market.

    Sentiment: Strong Buy

  • Reply to

    The forgotten trial

    by kadaicher1 Oct 30, 2014 2:49 PM
    kadaicher1 kadaicher1 Nov 1, 2014 10:05 AM Flag

    Patients in that old trial were also checked for APOE4 and it was over represented in both arms, but no differences in results were observed.
    "Metal-Protein Attenuation With Iodochlorhydroxyquin (Clioquinol) Targeting Aβ Amyloid Deposition and Toxicity in Alzheimer Disease"

    Sentiment: Strong Buy

  • Reply to

    The forgotten trial

    by kadaicher1 Oct 30, 2014 2:49 PM
    kadaicher1 kadaicher1 Nov 1, 2014 7:17 AM Flag

    Hi ITM, I hope you are correct. Now PBT1 is a different MPAC, but at the same time it is very close to PBT2. PBT2 was shown to be superior. The 2003 PBT1 trial, at 36 patients, was not so much smaller than IMAGINE, and the placebo was 50% at 18 patients. All patents were on Aricept for at least 6 months. They ran an extension trial of 18 months with all on Aricept.
    That trial used ADAScog results at baseline, not biomarkers, to separate the advanced stage Alzheimer's from the moderate stage patients (

    Sentiment: Strong Buy

  • Reply to

    Failed to deliver final report?

    by brewman228 Oct 31, 2014 5:32 PM
    kadaicher1 kadaicher1 Oct 31, 2014 11:20 PM Flag

    ASX regulations are that price sensitive news cannot be released at the AGM. It must be released to the market first. I am tipping a big news event either right before or right after the AGM. Before the report.

    Sentiment: Strong Buy

  • Reply to

    The forgotten trial

    by kadaicher1 Oct 30, 2014 2:49 PM
    kadaicher1 kadaicher1 Oct 31, 2014 12:32 AM Flag

    So with a tiny or no cognition loss it was very difficult to demonstrate any positive results in IMAGINE. This early trial demonstrated a strong signal of efficacy with advanced patients. I would have been happier if Prana had offered some patients in the extension trial increased dosage as seen in this early trial.
    Also with more advanced patient perhaps there was a measurable cognition loss in the placebo to compare against, and probably less chance of placebo effect distorting results.
    (STUDY DESIGN
    The study was a double-blind, placebo-controlled, parallel-group randomized design. Thirty-six patients and their caregivers were recruited. The duration of the study was 36 weeks. The oral dosage of clioquinol was 125 mg twice daily from weeks 0 to 12, 250 mg twice daily from weeks 13 to 24, and 375 mg twice daily from weeks 25 to 36.)

    Sentiment: Strong Buy

  • kadaicher1 by kadaicher1 Oct 30, 2014 2:49 PM Flag

    This was in moderately severe Alzheimer disease. Remember it works better in the more advanced patients. The IMAGINE trial tried to show effect in early stage patients, but we have already seen the effects in more advanced patients, and results were good. PBT2 is an analog of Clioquinol. Prana also owns the IP for Clioquinol in the USA for AD.
    PBT2 off label use after HD approval could go into the mod/ severe space, and could prevent or delay full care.
    Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial.
    Ritchie CW1, Bush AI, Mackinnon A, Macfarlane S, Mastwyk M, MacGregor L, Kiers L, Cherny R, Li QX, Tammer A, Carrington D, Mavros C, Volitakis I, Xilinas M, Ames D, Davis S, Beyreuther K, Tanzi RE, Masters CL.
    Author information
    Erratum in
    Arch Neurol. 2004 May;61(5):776.
    Abstract
    OBJECTIVE:
    To test this theory, we developed a clinical intervention using clioquinol, a metal-protein-attenuating compound (MPAC) that inhibits zinc and copper ions from binding to Abeta, thereby promoting Abeta dissolution and diminishing its toxic properties.
    METHODS:
    A pilot phase 2 clinical trial in patients with moderately severe Alzheimer disease.
    RESULTS:
    Thirty-six subjects were randomized. The effect of treatment was significant in the more severely affected group (baseline cognitive subscale score of the Alzheimer's Disease Assessment Scale, /=25), due to a substantial worsening of scores in those taking placebo compared with minimal deterioration for the clioquinol group. Plasma Abeta42 levels declined in the clioquinol group and increased in the placebo group. Plasma zinc levels rose in the clioquinol-treated group. The drug was well tolerated.
    CONCLUSION:
    Subject to the usual caveats inherent in studies with small sample size, this pilot phase 2 study supports further investigation of this novel treatment strategy using a metal-protein-attenuating compound

    Sentiment: Strong Buy

  • Reply to

    Beating a dead...

    by copper725 Oct 29, 2014 11:00 AM
    kadaicher1 kadaicher1 Oct 30, 2014 1:42 PM Flag

    As Copper rightly emphasized there are still a lot of unknowns around those processes, but you do not have to scratch very deep to find an indication PBT2 is probably capable of effecting Ca2+ levels.
    From the preclinical work which demonstrated PBT2 can strengthen dendretic spines
    ( CamKII was elevated (+57%, p = 0.005) following PBT2 treatment.)
    Regulating chemicals for CamKII are Ca2+ and calmodulin(CaM), with Ca2+ activating the CaM switch .
    It is not so surprising PBT2 could be working on a calcium ion, considering calcium is also a metal.
    Zn and Cu have been shown in other research as incapable of affecting the on-off switching ability of calmodulin.
    ( it was found that all cations examined with ionic radii close to or greater than that of Ca2+ induced the formation of the CaM–metal–M13 ternary complex, whereas those with smaller ionic radii were not effective, or much less so. )

    My opinion is that studies on calcium ions in neurodegeneration are very relevant to Prana and MPACs.

    Sentiment: Strong Buy

  • Reply to

    Beating a dead...

    by copper725 Oct 29, 2014 11:00 AM
    kadaicher1 kadaicher1 Oct 30, 2014 11:41 AM Flag

    ITM, please keep any info coming. Neurodegeneration is such a complex field. I do not get as much time for research these days and your posts provide some great material. Your, and others posts, save me a lot of time and I am sure I am not the only investor who thinks this way.

    Sentiment: Strong Buy

  • Reply to

    FInancials out

    by interestingtome Oct 30, 2014 6:23 AM
    kadaicher1 kadaicher1 Oct 30, 2014 11:25 AM Flag

    I guess expenses on the extension trial will ramp up a little as end of trial testing and imaging is done. I hope the "something else" is rushing the Parkinsons/movement disorder drug to trials. Maybe the brain cancer drug is now going through toxicity. I guess there will be much less restrictions on increasing dose levels in advanced brain cancer patients. For someone losing that battle the risk is worth it, but mostly I hope Prana can provide at least another incremental step in the fight against brain cancer. I did not see the last ASCO publications, but there was a lot of research reported the previous year for very little to no gain.

    Sentiment: Strong Buy

  • Reply to

    What are we looking for to move this.

    by kadaicher1 Oct 29, 2014 3:11 PM
    kadaicher1 kadaicher1 Oct 30, 2014 12:30 AM Flag

    ITM, I think your opinion on that is right on the money. I thought the trial was too small to prove much except plaque removal, and it even proved too small for that, when a few outstanding placebo patients were enough to wreck the placebo trend, compared to historical trends from previous larger trials. Considering the placebo effect on the brain could have a strong effect by changing an attitude to positive and giving hope, starting exercise, eating smarter and improving sleep patterns. These are all things that have emerged as helping, either just before or during the IMAGINE trial.
    Then as you pointed out there is APOE4. All considered a nightmare to design a small trial around.

    Sentiment: Strong Buy

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