The "Image study" had originally total 42 cases, 1/3 in the placebo group (= 14 cases). To demonstrate 20% effect in PET scan only 7 cases in a group is needed but if 10% effect in Pet scan is expected almost 30 cases is needed. ( follow-up is 1y). So Prana expects better than 10% effect and I think that the effect is much stronger than that. When you compare the numbers of the future Lilly's Sola study the difference is huge. They need some 2000 cases. Of course the target is different, Sola needs to demonstrate efficacy in cognition but PBT2 has already done that part ( only in 3 month study) but now Prana wants to demonstrate effecacy in the images (and of course also in cognition in 1y study). Masters's presentation 3 y ago explained well the power calculations when dealing with PET scan but perhaps even more interesting imaging modality will be MRI after the mouse studies have demonstrated strong regeneration of brain tissues. Those power calculations are not known to us but the Prana scientists have them and they know that 12-14 cases are enough, perhaps less. When only 2 patients were lost in the study, I expect very powerful results. And we have already seen one case and his wife.
pivotalchange, thank you for your table of new drugs. It gives a good basis to consider what new drugs will cost. New drugs are expensive and many of them do not even give lot of help to the patient but there are also some excellent drugs. Just looking at the Kelvin Lawler video I am convinced that PBT2 will be one of the excellent ones. It does not only help one person with AD but also the care taker.
Your 24B is based that there would be only 2M patients taking the drug and sure it could be year 2019 or later before PBT2 gets to this level.
Prana tells in it's AGM last month that "Drugs with Orphan drug status have exclusivity for a defined period and can command much higher product price". IMO this is an indication that the price of PBT2 will not be at the cheap end of the list of new drugs and HD will be the first indication for PBT2. But at the same time I think that there will be patients buying PBT2 with their own money to treat their memory or AD. To get maximal number of these buyers the price needs to be still "reasonable".
- 36-40M AD patients in the world, 5M in US, numbers increasing
- now cost of caring AD patients in US is 203B, in the world some 1 T, numbers increasing
- now unpaid help 216B in US, in the world some 1T, numbers increasing
- read what zhidao90 wrote on the board yesterday, there are millions like zhidao
- look at the Australian video about the AD patient on PBT2 over 1y, compare it with zhidao's dad
- extrapolate " the old but normal mouse study" to humans, very likely similar mechanism
- new brain drugs are expensive, even $70.000/y and they give only little help
What I try to say that the cost of AD is huge at the moment and so is the suffering of the patients and their care takers. It can be that PBT2 could reduce both of these if the Image and HD study will give us good results. It is difficult to figure out worth of PBT2 reducing human suffering of the patients and care takers but just looking the present paid and unpaid help I think PBT2 can get a reasonable price. Looks like treatment of a single AD patient costs now in US some 80K+ all suffering.
Improving age related memory loss is more difficult to estimate. It could be compared with plastic surgery or even buying of a smart phone. 20y ago nobody thought that every man and woman in the world would need a mobile phone. I would like to think that equal to this it could be that also every old human being would like to have as smart brain as possible. If PBT2 helps in this, it could be equal popular as it is today to use mobile phones.
Zapalz, thanks! That abstract did not tell anything about normals living longer when on PBT2. Unfortunately I do not have opporturnity to read the paper but only the abstract. Anyhow I am sure we had this study reporting longer life of normal mice on PBT2. We even had some discussion about this few years ago here on this board. Brain controls very many important things in our body but old brain cannot do anymore everything it should and so we will get problems. The metal balance is not only important in the brain but also in other organs as hearts.
Prana had few years ago a poster about HD and PBT2 in HD mouse model. If I remember it right there was also a normal mouse group getting PBT2 and those mice lived longer than the normal mice without PBT2. Does anybody else remember this poster or is that it was only the HD mouse group living longer. When we got this study as publication there was not at all this normal mouse group getting PBT2. I just wonder if I remember this right because nobody has been talking if PBT2 has this effect. The last Adlard's paper did not have similar group.
I think that the study with "old mice" is the very basic study of all including Reach2H and Image and the first Ph2 study. The "normalisation" of metal balance happens also in spite there is accumulating amyloid plaques or huntingtin monomers and at the same time PBT2 clears these accumulating toxines. And in each case we will get more synapses, neurons, etc with better memory.
Yes, I made these mistakes. $200B is the right target for PBT2. The problem is that here in Europe Milliard is same as Billion.
Simonig and others, I just wonder how do you get the figure $20 Billion a year ?? It can be a figure how much all Alz drugs are selling at present, but it has nothing to do with a disease modifying drug what we have in PBT2 . I admit that we still need the results but everything we have today is demonstrating that PBT2 is a disease modifying drug and not only in AD but also in HD and in normal physiological loss of memory in those over 50y old.
So IMO we need to add a lot to this $20 because PBT2 is a very different drug world has ever seen. It improves the function of brain. Most likely it will be a $200M /y drug !! Untill now we have only been able to turn brain function down with alcohol, barbiturates, neuroleptics, sleeping pills, many depression medications (not all) etc. So the list of indications for PBT2 will be very long. We need the results but PBT2 is not only a drug to be used in AD. At the moment it looks like we will benefit of it when getting over 50y old. Of course (if successful) PBT2 will replace most of present AD drugs and so 20M will be the first target, but PBT2 will be much more.
Thank you Dogs...Anybody who has been dealing with an AD patient knows how the "clock" is not working in these patients. But I think that this "Clock"- problem can be extrapolated to sleeping problems, which are very common in any population and increasing by age. I am almost sure that it is due to brain degeneration in many cases. It is treated now by putting the brain down with sleeping pills. May be not the smartest way, but we have not yet PBT2 in the pharmacy to stop the brain degeneration and reverse the degeneration. So I would say that in the future PBT2 or may be it's modification will be used as a different sleeping pill which also helps the cause of the sleeping disoder.
Sentiment: Strong Buy
IMO Prana is still science driven company also when you look at the pps. We had the first Ph2 results in 2008, later in 2011 the famouse AD mouse study by Adlard, another one last month etc, always with a sudden increase in pps. When there is no science news pps will go down. Investment bank recommendations have had almost no or very small effect. Their recommendation for pps has been for years $6 within the next year. So we need only wait the HD and AD study results and without them (or other possible science news) the pps will go up and down perhaps as technical analysis tells it to go (??). IMO only after these results early next year, there will be new situation. Then the recommendations by fools and others can be stronger (depending on results) without telling that the risk is very high. Investment banks can be even more conservative in their recommendations than the pharma companies in giving credit to Prana's science. Next year we will also get AD mannequins from the AD extension study to convince that the p values in research have also credibility in real life. Only after March there can be made real calculations of the value of Prana. Because I believe in p values and even many mouse study results, I have been adding Prana to my portfolio even at these levels. Age related memory paper by Adlard is worth of billions but fools neither big investment banks can understand it.
We have AGM on Thursday. I just wonder if they could have there any news to tell. Usually there has not been, but it is the only meeting when the owners meet the directors and so some questions could be asked.
Sentiment: Strong Buy
PLoS One. 2013 Nov 12;8(11):e79316.
The Zinc Transporter, Slc39a7 (Zip7) Is Implicated in Glycaemic Control in Skeletal Muscle Cells.
Myers SA, Nield A, Chew GS, Myers MA.
Collaborative Research Network and the School of Health Sciences, University of Ballarat, Mount Helen Campus, Victoria, Australia.
Dysfunctional zinc signaling is implicated in disease processes including cardiovascular disease, Alzheimer's disease and diabetes. Of the twenty-four mammalian zinc transporters, ZIP7 has been identified as an important mediator of the 'zinc wave' and in cellular signaling. Utilizing siRNA targeting Zip7 mRNA we have identified that Zip7 regulates glucose metabolism in skeletal muscle cells. An siRNA targeting Zip7 mRNA down regulated Zip7 mRNA 4.6-fold (p = 0.0006) when compared to a scramble control. This was concomitant with a reduction in the expression of genes involved in glucose metabolism including Agl, Dlst, Galm, Gbe1, Idh3g, Pck2, Pgam2, Pgm2, Phkb, Pygm, Tpi1, Gusb and Glut4. Glut4 protein expression was also reduced and insulin-stimulated glycogen synthesis was decreased. This was associated with a reduction in the mRNA expression of Insr, Irs1 and Irs2, and the phosphorylation of Akt. These studies provide a novel role for Zip7 in glucose metabolism in skeletal muscle and highlight the importance of this transporter in contributing to glycaemic control in this tissue.
So you seem to think this analysis is done by the students. Could be but now at least under good supervision by real professionals. Data entry was also done during the summer when universities are also closed so perhaps I do not think this work is done only when there are classes. But this data entry in July-Sept was not done correctly ( by the students??) so I think there are now some more professional people doing the job. By now the data entry must be completed because it cannot last more than 5 months. There was only some 100 patients ( speed 1 patient data per day )
In any case I understand now that nowbody seems to know "When is early 2014". Neither do I but just speculating how all this time is used without getting anywhere yet and perhaps not before February or March.
Is it early Jan ?, possible still Feb ?, but not March ? ( when we have Image results) or already Dec 2013???
How they got this "early 2014" ? Was Prana promised to get the results by X-mas, because after X-mas there is not much happening anyhow (holiday time) and so Prana took some additional days and so we got this "early 2014" ???. If so, could we in fact get them "late 2013" ???. Perhaps not but perhaps possible???
It is today 10wks when the problem was announced to us, evidently it was found by the researchers and by Prana 1 week earlier, then discussed about the solutions and consequenses. So "early 2014" was the result of these discussions. If "early 1014" means first weeks of Jan, 2014, we need to wait still some 6-7 weeks. That would mean that the reachers would have totally 16-17 weeks time (after this September announcement) to get the results. It is a very long time. Originally the plan was to get the results in Oct after completing the data collection in late July. So now with this extended waiting for these results is actually 4-5 weeks longer than the original plan was.
It could be that the problem was so big that they really needed this longer time, but I think it could be just the opposite and not all the work done during 7-8 weeks in July-Sept was not lost but biggest part was perhaps O.K. Everything had to checked but still.
"Early 2014" is perhaps a safe expression. It must mean that we will get the results in very first weeks in January, but there is also some possibilities to get them early, even before x-mas.
Sentiment: Strong Buy
"Our results suggest that the reduction in ferroportin levels are likely associated with cerebral ischaemia, inflammation, the loss of neurons due to the well-characterised protein misfolding, senile plaque formation and possibly the ageing process itself. The reasons for the reduction in hepcidin levels are less clear but future investigation could examine circulating levels of the peptide in AD and a possible reduction in the passage of hepcidin across damaged vascular endothelium. Imbalance in the levels and distribution of ferritin light-chain further indicate a failure to utilize and release iron by damaged and degenerating neurons"
Acta Neuropathol Commun. 2013 Sep 3;1(1):55.
The systemic iron-regulatory proteins hepcidin and ferroportin are reduced in the brain in Alzheimer's disease.
Raha AA, Vaishnav RA, Friedland RP, Bomford A, Raha-Chowdhury R.
John Van Geest Centre for Brain Repair, Department of Clinical Neuroscience, University of Cambridge, Cambridge CB2 0PY, UK. email@example.com.
The pathological features of the common neurodegenerative conditions, Alzheimer's disease (AD), Parkinson's disease and multiple sclerosis are all known to be associated with iron dysregulation in regions of the brain where the specific pathology is most highly expressed. Iron accumulates in cortical plaques and neurofibrillary tangles in AD where it participates in redox cycling and causes oxidative damage to neurons. To understand these abnormalities in the distribution of iron the expression of proteins that maintain systemic iron balance was investigated in human AD brains and in the APP-transgenic (APP-tg) mouse.
Protein levels of hepcidin, the iron-homeostatic peptide, and ferroportin, the iron exporter, were significantly reduced in hippocampal lysates from AD brains. By histochemistry, hepcidin and ferroportin were widely distributed in the normal human brain and co-localised in neurons and astrocytes suggesting a role in regulating iron release. In AD brains, hepcidin expression was reduced and restricted to the neuropil, blood vessels and damaged neurons. In the APP-tg mouse immunoreactivity for ferritin light-chain, the iron storage isoform, was initially distributed throughout the brain and as the disease progressed accumulated in the core of amyloid plaques. In human and mouse tissues, extensive AD pathology with amyloid plaques and severe vascular damage with loss of pericytes and endothelial disruption was seen. In AD brains, hepcidin and ferroportin were associated with haem-positive granular deposits in the region of damaged blood vessels.
" Conclusions: high folate or folic acid supplements may be detrimental to cognition in older people with low vitamin B12 levels. This topic is of global significance due to the wide distribution of food fortification programs, so prospective studies should be a high priority".
J Alzheimers Dis. 2013 Nov 18. [Epub ahead of print]
Among Vitamin B12 Deficient Older People, High Folate Levels are Associated with Worse Cognitive Function: Combined Data from Three Cohorts.
Moore E, Ames D, Mander A, Carne R, Brodaty H, Woodward M, Boundy K, Ellis K, Bush A, Faux N, Martins R, Masters C, Rowe C, Szoeke C, Watters D.
The University of Melbourne, Department of Psychiatry, Parkville, VIC, Australia Barwon Health, Geelong, VIC, Australia.
Background: Folate fortification of food aims to reduce the number of babies born with neural tube defects, but has been associated with cognitive impairment when vitamin B12 levels are deficient. Given the prevalence of low vitamin B12 levels among the elderly, and the global deployment of food fortification programs, investigation of the associations between cognitive impairment, vitamin B12, and folate are needed. Objective: To investigate the associations of serum vitamin B12, red cell folate, and cognitive impairment. Methods: Data were collected on 1,354 subjects in two studies investigating cognitive impairment, and from patients attending for assessment or management of memory problems in the Barwon region of south eastern Australia between 2001 and 2011. Eligible subjects who had blood measurements of vitamin B12 and red cell folate taken within six months of cognitive testing were included. Subjects with stroke or neurodegenerative diseases other than Alzheimer's disease were excluded. A Mini-Mental State Examination score of 1,594 nmol/L) levels were more likely to have impaired cognitive performance (adjusted odds ratio (AOR) 3.45, 95% confidence interval (CI): 1.60-7.43, p = 0.002) when compared to participants with biochemical measurements that were within the normal ranges. Participants with high folate levels, but normal serum vitamin B12, wer