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Prana Biotechnology Limited Message Board

pivalde 101 posts  |  Last Activity: Feb 11, 2016 2:09 AM Member since: Feb 15, 2001
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  • Jan 29, 253.934 shorted, less than for a very long time. Looks like not many are expecting to get lower levels from here.

  • pivalde pivalde Jan 31, 2016 2:08 PM Flag

    The divident will come every year, only bigger and bigger !

  • J Aging Health. 2016 Jan 26. pii: 0898264315624899. [Epub ahead of print]

    Cost of Dementia and Its Correlation With Dependence.

    �kerborg �1, Lang A2, Wimo A3, Sk�ldunger A3, Fratiglioni L4, Gaudig M5, Rosenlund M6.

    OBJECTIVE:

    To estimate the cost of dementia care and its relation to dependence.

    METHOD:

    Disease severity and health care resource utilization was retrieved from the Swedish National Study on Aging and Care. Informal care was assessed with the Resource Utilization in Dementia instrument. A path model investigates the relationship between annual cost of care and dependence, cognitive ability, functioning, neuropsychiatric symptoms, and comorbidities.

    RESULTS:

    Average annual cost among patients diagnosed with dementia was #$%$43,259, primarily incurred by accommodation. Resource use, that is, institutional care, community care, and accommodation, and corresponding costs increased significantly by increasing dependency. Path analysis showed that cognitive ability, functioning, and neuropsychiatric symptoms were significantly correlated with dependence, which in turn had a strong impact on annual cost.

    DISCUSSION:

    This study confirms that cost of dementia care increases with dependence and that the impact of other disease indicators is mainly mediated by dependence.

  • Reply to

    Comparison of AD-in-a-Dish and MRI texture

    by pivalde Jan 17, 2016 10:07 AM
    pivalde pivalde Jan 30, 2016 1:20 PM Flag

    Just returning to this texture measurement / volume issue. In fact both methods use a computer program about the same MRI picture to get the volume and texture measures. So only the computer program is different but the image ( which is also a result of computing) and the information the image is based is the same. So even the texture measure is an ad hoc analysis it is based just on the same information MRI device has already collected to make the visible image and from which information the hippocampus volume has been computed. So this is how the image diagnostics goes forward, we can make also something else than images from the information collected for an image.

  • Reply to

    A quarter of a decade

    by goutah3006 Jan 30, 2016 10:39 AM
    pivalde pivalde Jan 30, 2016 12:03 PM Flag

    Yes goutah, it is even worse than that, because Huntington's disease has been recognised as a disoder since Middle Ages and G Huntington made description of the problem as early as in 1872. Since those times much of effort has been done to help these patients and still today we need to wait perhaps an other month or two if PBT2 can be used in a clinical test in USA at a dosage above 250mg/day. As you know in Europe there are more HD cases than in USA and there there is not any clinical hold. Orphan status has been granted for PBT2 both in USA and Europe and ph2 study demonstrated cognition improvement in 6 months at dosage of 250mg and when tested on a higher dosage the effect was even stronger accoding the AGM. We been informed that Prana will get it's report to FDA done in early 2016 and most likely FDA will give it's reply in following 30 days. So it has been very long time to get any disease modifying drug to HD patients but now there is a hope for them at least for cognition problems if the new Ph3 study will confirm the results of the earlier experiment. The study will be done but if there are any USA patients in the study is still open.

  • This paper is now published:

    ACS Chem Neurosci. 2016 Jan 20;7(1):119

    Clioquinol Improves Cognitive, Motor Function, and Microanatomy of the Alpha-Synuclein hA53T Transgenic Mice.

    Finkelstein DI1, Hare DJ1,2,3, Billings JL1, Sedjahtera A1, Nurjono M1, Arthofer E1,4, George S5, Culvenor JG5, Bush AI1, Adlard PA1.

    Abstract

    The abnormal accumulation of alpha-synuclein (α-syn) has been linked to a number of neurodegenerative disorders, the most noteworthy of which is Parkinson's disease. Alpha-synuclein itself is not toxic and fulfills various physiological roles in the central nervous system. However, specific types of aggregates have been shown to be toxic, and metals have been linked to the assembly of these toxic aggregates. In this paper, we have characterized a transgenic mouse that overexpresses the A53T mutation of human α-syn, specifically assessing cognition, motor performance, and subtle anatomical markers that have all been observed in synucleinopathies in humans. We hypothesized that treatment with the moderate-affinity metal chelator, clioquinol (CQ), would reduce the interaction between metals and α-syn to subsequently improve the phenotype of the A53T animal model. We showed that CQ prevents an iron-synuclein interaction, the formation of urea-soluble α-syn aggregates, α-syn-related substantia nigra pars compacta cell loss, reduction in dendritic spine density of hippocampal and caudate putamen medium spiny neurons, and the decline in motor and cognitive function. In conclusion, our data suggests that CQ is capable of mitigating the pathological metal/α-syn interactions, suggesting that the modulation of metal ions warrants further study as a therapeutic approach for the synucleinopathies.

  • Reply to

    Stryker/ Bio4 expansion continues

    by nsubzac Jan 27, 2016 3:00 AM
    pivalde pivalde Jan 27, 2016 7:20 AM Flag

    Over 30 indications just for foot and ankle surgeons !!

  • PLoS One. 2016 Jan 25;11(1):e0147488. doi: 10.1371/journal.pone.0147488.

    Effect of Copper and Zinc on the Single Molecule Self-Affinity of Alzheimer's Amyloid-β Peptides.

    Hane FT1, Hayes R2, Lee BY1, Leonenko Z1,2.

    Abstract

    The presence of trace concentrations of metallic ions, such as copper and zinc, has previously been shown to drastically increase the aggregation rate and neurotoxicity of amyloid-β (Aβ), the peptide implicated in Alzheimer's disease (AD). The mechanism of why copper and zinc accelerate Aβ aggregation is poorly understood. In this work, we use single molecule force spectroscopy (SMFS) to probe the kinetic and thermodynamic parameters (dissociation constant, Kd, kinetic dissociation rate, koff, and free energy, ΔG) of the dissociation of an Aβ dimer, the amyloid species which initiates the amyloid cascade. Our results show that nanomolar concentrations of copper do not change the single molecule affinity of Aβ to another Aβ peptide in a statistically significant way, while nanomolar concentrations of zinc decrease the affinity of Aβ-Aβ by an order of magnitude. This suggests that the binding of zinc ion to Aβ may interfere with the binding of Aβ-Aβ, leading to a lower self-affinity.

  • pivalde pivalde Jan 23, 2016 4:38 AM Flag

    New drugs in MS cost some $100 / pill (daily pill). So in AD the cost could roughly be at be same level. You could get to 3 billion if only a small % of AD patients buys the drug. AD takes some 20y to develop and I would think that some of these 100 millions would like to take a preventive drug. Figures can get to astronomical levels but before PBT2 gets there there is some work to be done.

  • This is a free paper indicating interesting possibilities for the over 2000 MPACs of Prana. MPACs are not only for neurodegeneative diseas or cancers but also for many different types of diseases as cardiomyopathies.

    Cardiovasc Diabetol. 2014 Jun 14;13:100. doi: 10.1186/1475-2840-13-100.

    Diabetic cardiomyopathy is associated with defective myocellular copper regulation and both defects are rectified by divalent copper chelation.

    Zhang S, Liu H, Amarsingh GV, Cheung CC, Hogl S, Narayanan U, Zhang L, McHarg S, Xu J, Gong D, Kennedy J, Barry B, Choong YS, Phillips AR, Cooper GJ1

  • Reply to

    Comparison of AD-in-a-Dish and MRI texture

    by pivalde Jan 17, 2016 10:07 AM
    pivalde pivalde Jan 21, 2016 1:59 PM Flag

    wcamp, I agree. However Sörensen's method was tested already in this first paper in 3 different populations: ADNI, AIBL and Copenhagen metropolitan population. Totally in 836 patients and also in ADNI subsets with CFS analysis and ADNI FDG-PET subset ( measuring hippocampus metabolic rate of glucose). It was demonstrating excellent generalization performance ( in the inventor's hands). So to me it looks very promising, but it needs to be tested by others aswell.
    What comes to post hoc analysis of Imagine population. In fact I think that when you use the same MRI images as before, it is not at all a big stretch, just an other way of analysing them. But this is new to FDA aswell as to Prana and equally to big pharma. In any case the method seems to improve the sensitivity of MRI scans in comparison to volume, the best prognostic measure before we got this texture. IMO texture could be well accepted as a tool to study efficacy of AD and HD drugs.

  • Matlack KE et al :
    "CQ dramatically reduced Aβ peptide levels in a copper-dependent manner by increasing degradation, ultimately restoring endocytic function. This mirrored its effects on copper-dependent oligomer formation in vitro, which was also reversed by CQ. This unbiased screen indicates that copper-dependent Aβ oligomer formation contributes to Aβ toxicity within the secretory/endosomal pathways where it can be targeted with selective metal binding compounds".
    So if you thought that copper wants to be bad only here on the board, you need to know that coopper is bad also in brain, it causes alzheimer disease by increasing formation of toxic oligomers and clioquinol ( as PBT2) can help. So it looks it will take some time before we will get rid of copper here on the board and from AD brain but sure when PBT gets to the market copper will disappear from the board and also from the brains of many milloins brains.
    It is important to notice that clioquinol can resore the endocytic function to get rid of toxic oligomers and IMO that is why the Euro-study and Reach2HD study demonstrated improvement of cognition (?).
    As long we have copper here on the board it will be bad as it will be bad also in the brain. Copper is needed elsewhere, not here on the board and neither too much in anybodies brain where it is really bad, bad.

  • Reply to

    Comparison of AD-in-a-Dish and MRI texture

    by pivalde Jan 17, 2016 10:07 AM
    pivalde pivalde Jan 17, 2016 4:02 PM Flag

    kadaicher, I did not see his comments, but I know that he got my e-mail and responded somehow to it so that I got a positive feedback. But who would not be interested about a method which gould make the "failed Imagine study" to a success, worth of millions, when you own some 5% of the company.
    The problem with volume measurements is weak sensitivity. It cannot find small changes as texture does. In the Sörensen paper volume measures were not at all correlated with early lowering of cognition but texture was ( p smaller than 0.001). Texture looks to have the sensitivity needed to find if PBT2 will slow down degeneration speed in 1y . Volume will only srink after there is already quite a lot of degeneration but texture will pick up even these smaller changes. But we are not yet there. Sörensen needs to measure the Imagine study MRI scans to prove if my strong believes are true, that PBT2 really slows down the degeneration speed of the hippocampus of MCI patients.

  • Tanzi's letter in AGM tells as preliminary findings: " PBT2 has the following effects in Alzheimer’s-in-a-Dish: 1. A trend in the direction of attenuation of the aggregation and fibrillization of the Abeta peptide into beta- amyloid, 2. significantly reduced tangle formation, and 3. significantly increased cell viability.
    MRI texture classifies "intensity variation" and "structure" which are related to 1) healthy neurons, 2) formation of Abeta plaques and NFTs and 3) neuronal death 4) normal or abnormal size/shape of the structure as a schematic view. In reality texture scores are kind of concatenated filter responce histograms about the MRI image. But by being a very sensitive tool in early neural degeneration it looks like it will just capture similar things as Tanzi in his dish: early aggregation and fibrillation of Abeta, reduced tangle formation and perhaps even increased cell viability (???). The difference is perhaps "only" the fact that in texture analysis we can have real patients.
    To me it looks like it is now possible to see almost the same as some of us are waiting to see to happen in Tanzi's dish but in real patients and in fact in a controlled study = the Imagine study. To me it looks like that even the number of placebo treated (15) will be enough ( I hope I am right) because the sensitivity of texture analysis is so much better than measuring hippocampal volume resulting already statistical trend and 35% reduction of hippocampal atrophy. All the MRI scans are ready for that analysis. Kempler will for sure send the pictures to Sörensen, at least I would send if I would be the CEO of Prana. Sörensen et al can do the needed work in few days, only 41 cases. If this works how I think it will, everybody will soon see how valuable the Imagine study was in the end ( perhaps few billions????).

  • pivalde pivalde Jan 15, 2016 8:30 AM Flag

    PET scan will be "obsolet" in diagnostics (?) and in the follow-up of AD. Big pharma is still using PET scan because they never did an Imagine study to understand it's poor value . Perhaps it is still used when looking the risk factors, but for that purpose it is too expensive IMO. AD studies will be much cheaper to do in future and an individual clinical progress can be followed easily. I am sure the method becomes even more accurate in future and Sörensen et al has lot of work indeveloping their method.
    The next AD study with PBT2 can be much smaller than thought earlier to confirm once again it's efficacy but to find all possible side effects a relative big population is needed. In any case imaging costs will be down a lot.

  • pivalde pivalde Jan 15, 2016 3:39 AM Flag

    Kempler and Prana research team know the article by Sörensen et al about hippocampal texture. I sent it to them and they appreciated it in an e-mail to me. After all disappointments with the Imagine study I would think that they are already in contacts with the Danish group, but I do not know if anything is happening. When by measuring volumes the atrophy speed was reduced as much as 35% by PBT2 and still statistically the difference was not singnificant ( only a trend) the reason must be poor sensitivity of the measuring tool and not only the small number of patients. 35% is a lot !!
    In the Sörensen paper the volume was not at all correlated with cognition in early stages of dementia but texture was strongly (p smaller than 0.001). To me it looks like that hippocampal srinking happens later and in fact it is very natural. So it could be that vol srinking still continues for a while at the same speed as earlier in spite PBT2 treatment has already been started and stopping further degeneration. So the difference in texture analysis could be even more than 35%. But this is only my speculation.
    There is a similar need to study MRI texture in HD. Originally Sorensen published the method in COPD so to do the same in HD could be very much possible.

  • Reply to

    Partial Clinical Hold reminder

    by enigmatic6088 Jan 13, 2016 10:28 AM
    pivalde pivalde Jan 13, 2016 12:55 PM Flag

    goutah, I also have been waiting the extension study results but I think there will be only the safety results + the amyloid decrease in Pet scan the company has reported. The rest of it will be kind of speculative and will be speculated in the final paper one day because the numbers were even smaller than in the first year. My hopes were in the hippocampus vol srinking but now when I understand that the method of measuring it is quite poor ( AUC only 0.66 mesuring prognostics) I lost my hopes. This method cannot give in this small material any better results in spite 2y follow up. There would be too many false positives and false negatives. In such a small material you cannot have almost any of them. Sörensen's texture method has better AUC and if Prana will use it there is a possibility so see new results even from the first study year.But my guess is that the texture analysis will be used in future studies, most likely also in HD studies.
    However the main result of the Imagine study was that PET scan is not a tool to measure drug efficacy and that MRI has some potential. This means a lot of savings in the future AD studies.

  • Reply to

    PBT2 publications in 2015

    by pivalde Jan 12, 2016 3:17 PM
    pivalde pivalde Jan 13, 2016 12:08 PM Flag

    Yes, it would be a much longer list. These were the ones PBT2 was mentioned ( in the abstract).

  • Reply to

    Iron and Oxidative Stress in PD

    by pivalde Jan 12, 2016 3:39 PM
    pivalde pivalde Jan 12, 2016 4:14 PM Flag

    cont....
    Oxidative stress (TBARS and AOPP) and inflammatory markers (NTPDases, IMA, and myeloperoxidase) were significantly higher in PD, while antioxidants FRAP, vitamin C, and non-protein thiols were significantly lower in PD. The enzymes SOD, CAT, and ecto-5'-nucleotidase were not different among the groups, although NOx and ADA levels were significantly higher in the controls. Our data corroborate the idea that ROS/RNS production and neuroinflammation may dysregulate iron homeostasis and collaborate to reduce the periphery levels of this ion, contributing to alterations observed in the pathophysiology of PD.

  • On the last day in 2015 there were 257K shorted shares.

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