Hot Watch List (comments).
PRAN (neutral) 01.23.12 updated to buy; 03.16.13 updated to strong buy; 09.02.13 updated to hold before October; 11.17.13 updated to avoid or short
March 22, 2011 by BiotechInvest
Well, the "investomadness" attack happened again... This time it's about Prana "Alzheimer drug".
The publication of pre-clinical studies doubled PRAN pps in 1 day.
"MELBOURNE, AUSTRALIA--(Marketwire - 03/21/11) - Prana Biotechnology (NASDAQ:PRAN - News) (ASX:PBT - News) today announced the publication of new data on the ability of PBT2 to repair the damage in an Alzheimer's affected brain thereby facilitating the restoration of cognition in Alzheimer's Disease (AD). The findings help to explain the rapid improvement in cognition previously reported in transgenic Alzheimer's mice* and in patients in a Phase IIa clinical trial with PBT2**. The article published in the science journal PLoS ONE is entitled "Metal Ionophore Treatment Restores Dendritic Spine Density and Synaptic Protein Levels in a Mouse Model of Alzheimer's Disease."
After 11 days of treatment, the brains of the Alzheimer's mice showed a statistically significant increase in the numbers of spines on the branches (or dendrites) of neurons in the hippocampus, a memory centre specifically affected in AD. Increasing the number of spines is important as this permits many more neurons to interconnect with any particular neuron thereby increasing the brain's capacity to carry out learning and memory functions."
Guys, it's just about Alzheimer's mice... In this model numerous experimental drugs showed significant improvements.
They said in published paper:
"PBT2 treatment resulted in a robust increase in neurite outgrowth"
But there are many substances that can do itin vitro...
Read the paper before buy Prana for $4 (today price). I know it's a useless advice because many investors think that Prana discovered miracle drug against AD. It's too early to say that it's true or lie. Just Google for Neurochem Inc. (was NASDAQ NRM) and ALZHEMED™....
About Tramiprosate (ALZHEMED™)
Tramiprosate (ALZHEMED™) is a small, orally-administered molecule known as an amyloid B antagonist. Tramiprosate (ALZHEMED™) crosses the blood-brain-barrier, binds to soluble AB peptide and interferes with the amyloid cascade that is associated with amyloid deposition and the toxic effects of AB peptide in the brain. The presence of amyloid in the brain is one of the major histopathological characteristics of AD.
BTW NRM pps was around $5-6 before phase III trial failed.
Neurochem's new name, BELLUS Health Inc., which it expects to start using on April 21, 2008, together with the new stock ticker symbols. Now it's BLUS.PK with pps $0.12.
Unfortunately, can't short PRAN because TD said: "Shares of this security are currently not available to short sell."
Think twice before buy PRAN....
Since 1994, Prana scientists have contributed to over 100 peer-reviewed, high impact publications demonstrating how subtle defects in the metabolism of biological metals lie at the core of common neurodegenerative conditions. For Alzheimer's Disease (AD) in particular, this theory provides an elegant and consistent explanation for many of the otherwise disparate pathological phenomena associated with this condition.
While the principle of metal-mediated oxidative damage has broad relevance across a range of age-related neurodegenerative disorders, such damage is also observed in a diverse range of conditions and this suggests applicability of Prana MPACs to a variety of further diseases.
Prana's drug discovery and development platforms are based on "the metal theory" of Alzheimer's disease, which suggests key metals, such as zinc and copper, are responsible for the aggregation of beta-amyloid and the formulation of amyloid plaques. Both PBT1 and PBT2 were designed to reduce beta-amyloid accumulation.
The study enrolled 36 patients who were assessed for indicators of cognitive performance such as memory, orientation, language, attention and reasoning. The results were assessed using a cognitive score on the Alzheimer's disease Assessment Scale, the so-called ADAS-cog score. The scores range from 0 to 70, with lower scores indicating a healthy adult. As dementia progresses, the score increases. Eighteen of the patients were assigned to placebo and 18 received Prana's Alzheimer's disease drug, PBT-1 (Clioquinol) (the first of Prana's metal protein attenuating compounds (MPACs) to be developed for Alzheimer's disease). PBT-1 is a chemical that binds zinc and copper, and has been shown to lower the levels of A and the associated toxicity in the brains of Transgenic mice used as a model of Alzheimer's Disease.
The more affected patients entering Prana's pilot clinical trial (i.e. those with higher ADAS-cog scores) showed an average change in score at 24 weeks of about 1.5 points on PBT-1 and about 8.9 on placebo, a difference of 7.4. Generally, untreated patients with mild to moderate disease could be expected to gain six to 12 points in their ADAS-cog score over 12 months. A panel convened by the Food and Drug Administration in the US deemed an improvement of four points would be clinically significant.
"The results of this trial have been very encouraging to a clinician," said Dr Ritchie of UCL who led the study, adding; "Our findings have led to the development by Prana Biotechnology of new, possibly more effective drugs which hit the same target as Clioquinol. UCL plans to be involved in further testing of the principal using Clioquinol in a larger, UK multi-centre study which is seeking public funding."
Prana actually stated that zinc is a harmful (i.e. it helps to form toxic amyloid plaques) and their lead drug PBT1 due to its small size and solubility in lipid is able to enter the brain from the bloodstream and bind to zinc. Thus, PBT2 prevents the amyloid oligomer formation and can transfer the zinc and copper trapped in plaques into neurons to help promote normal functioning of nerve cells.
"Prana's therapeutic strategy is to restore normal metal levels and distribution in the brain, such as zinc, which typically changes with aging and is exacerbated in Alzheimer's Disease, resulting in (i) reduced synaptic function and (ii) beta-amyloid reacting with the metals to form toxic oligomers that impair cognition"
"Prana scientists have demonstrated that synaptic zinc can prevent APP from performing its normal iron transporting role. Synaptic zinc levels and distribution changes in the Alzheimer's diseased brain, because zinc released into the synaptic space is drawn into the beta-amyloid that forms plaques in the synapse. This is problematic for the brain because neurons are deprived of the zinc required for neurotransmission and the zinc induces toxic beta-amyloid oligomer formation. Moreover, as now indicated by the Cell publication, the zinc caught up in the beta-amyloid can be exchanged or transported to the APP, impeding its ability to prevent iron buildup in neurons. Accordingly, the maintenance of correct zinc levels in the brain is vital for neuronal function and ultimately cognition.
Prana's lead Alzheimer's drug, PBT2 acts as a zinc chaperone that transports zinc from the brain beta-amyloid deposits and returns it to neurons to facilitate normal neurotransmission. PBT2 has also recently been shown to have important neuroprotective and neurotrophic properties, consistent with its ability to prevent zinc from impairing the ability of APP to prevent iron overload."
So, Adeona wants to cure AD by simple elevating zinc concentration in AD brain but Prana wants to cure AD by slightly opposite method: to bind Zn, destroy toxic amyloid plaques and deliver Zn into neurons.
PBT2 had had some problem recently:
Toxicity Issues Halt PBT1 Program In Alzheimer's Prana's Stock Falls.
Prana received approval in January from the UK's regulatory agency for the 435-patient study to evaluate two dose levels of PBT1 (clioquinol) added to the existing therapy in patients with moderate Alzheimer's disease.
"Unfortunately, Prana needs to cancel the study," said Ivette Almeida, a spokeswoman for the Melbourne, Australia-based company, which is "planning to do a strategic review and investigation" of its PBT1 programs.
The company said it found "unacceptably high" levels of a toxic due impurity, believed to occur during the PBT1 synthesis. The impurity could cause an increased risk of side effects and mutagenicity.
Prana Biotechnology Plans to Advance Alzheimer's Clinical Trial
Who is right? Which strategy is more effective? Well, time will tell. Disclosure: I don't have PRAN positions. May be will short it if shares available. 01.23.2012 by BiotechInvest
It seems like that PRAN is a monopolist in development drug for Alzheimer's Disease:
MELBOURNE, AUSTRALIA--(Marketwire -12/15/11)- Prana Biotechnology (NASDAQ: PRAN - News) (ASX: PBT.AX - News) today announced that it has commenced recruitment and screening of patients for a 12 month Phase II Imaging trial testing PBT2, the Company's drug in development for Alzheimer's Disease. Screening of patients began last week with psychological tests to measure cognition(1). This week, the first patient was tested for evidence of significant levels of Abeta deposits in the brain(2). Professor Colin Masters, Prana consultant and Director of the Mental Health Research Institute, explained that "Prana is selecting patients with established Alzheimer's disease, as well as targeting those very early in the disease process. We are using the most modern techniques available for measuring PBT2's disease modifying effects to establish cognitive, functional and physical changes in the brain. By disease modifying, I mean modifying the rate of progress of Alzheimer's, slowing it down and delaying onset. We are using PiB-PET imaging to measure the drug's effects on the insoluble form of Abeta, and we are using a recently developed blood test to measure levels of the soluble oligomers of Abeta(3). This week we have been taking pre-drug dosing measures of eligible patients to compare with measures that will be taken throughout the trial. Per protocol, each patient qualifying for entry to the trial will receive the first dose of drug or placebo on their second visit to the clinic." "In my opinion PBT2 has the best and highest chance of all drugs currently in development to have a major impact on the disease process, and help avoid the global epidemic of Alzheimer's which, left untreated, is poised to become unmanageable. This trial that is now in progress will establish for the first time not only that PBT2 can improve cognition, as already shown, but that it can actually modify the course of the disease. It will be a major step forward if the drug demonstrates, as I think it will, its ability to affect both soluble and insoluble Abeta levels," concluded Professor Masters. MDVN Dimebon completely failed, LLI drug also failed, actually all big and small pharmas failed in AD drug R&D.
But U.S. wants effective Alzheimer’s treatment by 2025"Regardless, an estimated 5.4 million Americans already have Alzheimer’s or similar dementias — and how to help their families cope with day-to-day care is a priority, the advisory committee made clear Tuesday. The disease is growing steadily as the population ages: By 2050, 13 million to 16 million Americans are projected to have Alzheimer’s, costing $1 trillion in medical and nursing home expenditures. That doesn’t count the billions of dollars in unpaid care provided by relatives and friends."In simple words AD will bunkrupt USA by 2050...
Is effective AD treatment real by 2025? Nope...
With current NIH and NSF practice to give grants to distinguished old farters in science it's impossible.
When I see that another old farter got giant grant from NIH or from AA I only can wish him got AD
Just read it:
29 Years, $290 Million and Counting: Alzheimer's Association 2011 Grants
This year's international research grants support 78 best-of-field investigators from senior scientists to young and diverse investigators who are exploring disease mechanisms, risk factors, new clinical tools, and novel approaches to treatment and care.
And now read 2011 awards of AA :
I was a reviewer for AA and know that they never give grants to real talented young scientists, all grant selection process designed to reject them and give money to stupid projects.
The same situation is in NIH.
So, big pharmas failed and stop AD R&D, NIH and AA give money to stupid and useless projects and US government wants to get AD drug by 2025. Just absurd.
It's very unlikely that PRAN drug will cure AD. I's really sad because in 2025-50 many of us will have very high probability to get AD and there will not be cure for it.
But PRAN AD clinical trial may attract some interest from funds so small biotech investors may play with it.
Disclosure: I opened modest PRAN positions recently. May be I will add more if see that "big money" starts to accumulate PRAN.
03.16.2013 by BiotechInvest
Starting January 2012 I bought 20k PRAN shares (price range $1.53-1.89) and now average gain is 33%.
The truth is that PRAN is going much higher very soon. Especially after this news:
Prana Details Data Showing That PBT2 Reduces Cognitive Impairment Caused by Tau Protein Accumulation
Summary of New Data Presented at the 11th International Conference on Alzheimer's and Parkinson's Disease
Experimental MethodologyThe rTg(tauP301L)4510 mouse line6 is a transgenic mouse model of human tauopathy. From an early age rTg(taup301L)4510 mice display neurofibrillary tangles (NFT) like pathology in the neocortex which progresses into the hippocampus and limbic structures with increasing age. This is manifested biochemically by an age-dependent transition of accumulating tau species from soluble 55 kDa to insoluble hyperphosphorylated 64 kDa. The mice develop significant cognitive impairments from 4 months of age. In our study, rTg(tauP301L)4510 mice (n=10-15/group) were aged to approximately 12 months at which time they were administered either vehicle or PBT2 (30mg/kg) by daily oral gavage for six weeks. Prior to culling and tissue collection the cognitive performance of the animals was examined using a standard test of cognition, the Y-maze. A stereological analysis of NFT burden and neuron number was conducted by histology and other biochemical endpoints assessed by Western blot. ResultsAdministration of PBT2 resulted in significant improvement in performance in the Y maze, a significant reduction in the number of NFTs and a significant increase in cortical and hippocampal neurons in the rTg(tauP301L)4510 mouse model. A significant increase in the levels of the PP2A protein (implicated in tau phosphorylation events) in PBT2 treated animals suggest that the drug may directly act upon biochemical pathways which lead to NFT formation as well as any potential interaction with tau itself.Unfortunately >95% news readers didn't understand this "scientific" gibberish and news were passed unnoticeable. But not for me. PRAN scientists got perfect results but did wrong conclusions: "suggest that the drug may directly act upon biochemical pathways which lead to NFT formation as well as any potential interaction with tau itself".They should know that microtubule-associated protein (MAP) tau is inside of neurons (in axons) and drug should be membrane-permeable to interact with tau itself. PBT2 should be water-soluble to be a good chelator for Zn. It's very unlikely that PBT2 penetrates through axon membrane. So how PBT2 did "significant reduction in the number of NFTs and a significant increase in cortical and hippocampal neurons in the rTg(tauP301L)4510 mouse model"?The answer is simple: Alzheimer disease is complex one and there are two players - tau and toxic beta-amyloid species. Tau is starting disease - when it hyperphosphorylated tau detaches from axon microtubules (MT) and leave them unprotected.Microtubules are just railways for numerous trains (vesicles, mitochondria and etc.) that supply axon and synapses with food and building material. Tau is a rail guard (keep rails strong and not-damaged by cutter proteins). When tau detached from MT the rails are become damaged and trains movement slow down (fortunately there are multiple rails lines - microtubules bundle - by the way tau also is functioned as a glue for these bundles. Again when tau leave MT bundles become sparse and easy cut by katanin. Axon without supplies start to dying back, synapses are destroyed and Abeta peptides that is functioned in synapses are liberated in enormous amount. They form toxic Abeta deposits (plaques) near neurons and axons that increase permeability of neuron membranes to calcium ions. Ca2+ induces phosphorylation of healthy tau and all cycle repeated again. AD is cyclic disease when player #1 (tau) force player #2 (Abeta) to go in game. New (induced) player #2 agitates more players #1 that again attract more players #2 in the game. So, cascade amplification of players #1 and #2 and brain is destroyed. Big pharmas still trying to eliminate player #2 from game (Abeta) and sometimes successfully. But player #1 is still playing the game (may be slightly slower). May be PRAN PBT2 is just more effective in this game and eliminates more #2 players... The game become just slower.Well, It may slow down AD and decreasing of cognitive function. But to stop the game drug (or drugs) should eliminate both players with one shot. Or effectively target player #1 (tau) - change equilibrium to healthy unphosphorylated tau. It very hard problem. But it is doable. 08/30.2013 by BiotechInvestPRAN hit $5-6 range and still growing. New euphoria in AD area. My positions reach >100%. Question is: should I keep it through October? I don't think so... There is high probability that PRAN AD drug will fail to show any significant slow down of cognition decline as it was already many times when drug was designed to fight amyloid. So, may be it's a good idea to secure PRAN position by selling 50% at highest pps. 12/10/2013 I shorted PRAN at $7.15 - it seems like the company wants to fool investors with AD fake drug that "decrease amyloid level in patient brain" - phase II primary point. They hope that we forgot Neurochem failure with similar AD drug Alzhemed: "Alzhemed was designed as an anti-amyloid therapy. It is a patented variant of the amino acid taurine, which is reported to inhibit the interaction of Aβ with endogenous glycosaminoglycans and thereby prevent β-sheet formation. This drug originated in a screen for low-molecular-weight molecules that mimic glycosaminoglycans and can therefore antagonize the interaction of Aβ with endogenous glycosaminoglycans. Glycosaminoglycans have been shown to promote Aβ aggregation and plaque stability (Gupta-Bansal et al., 1995) has been proposed to interfere with amyloid fibril formation and deposition into plaques.
In vitro, Alzhemed was shown to preferentially bind soluble Aβ, inhibit Aβ aggregation and fibrillogenesis, and inhibit Aβ neurotoxicity (Gervais et al., 2001, Gervais et al., 2007). Treatment of TgCRND8 transgenic mice with systemic Alzhemed resulted in significant reduction (∼30 percent) in the brain amyloid plaque load (Gervais et al., 2007)." 30% decreased amyloid but did nothing with cognition decline in phase III trial. It looks like that all AD drugs that target amyloid were failed in trials. So PRAN will be next. So, it better avoid PRAN or short it at high before trial release. The results will be like "PBT2 significantly decrease beta-amyloid level in treated patients but there is no significant difference between control and treated groups in cognition decline" - phase III trial is needed. Neurochem and Medivation got very good results in phase II trials but both phase III were failed completely because the decreasing of beta-amiloid in AD patient brain will never cure AD. The best case scenario for PRAN will be that PBT2 will slightly slow a cognition decline in treated group in comparison with placebo one. It will mean that AD patients will die slower: instead of 7 years (last 2-3 of them be complete "vegetables") it will be 9 years. Will AD patient caregivers like such drug that prolong "vegetable" life 2-3 years more? It's very unlikely. Such drug will only add more economical burden for counties with highest lifetime. We need a drug for AD that will stop this terrible disease and actually cure it.
04/02/14 by BiotechInvest
PRAN story is finished, management continues lie about PBT2 and future trials but nobody believe them. Tanzi's "metal theory" of AD is completely failed.
I will transfer PRAN page in my archive and forget about this scam biotech.
09/04/15 by BiotechInvest
I'm still monitoring PRAN with purpose to make money on future "run up" events (for example start phase 3 clinical trial for HD). PRAN pps hit a historical low (below $0.87) and will continue decline but this scam biotech is still alive and there is some possibility to make some money.
10/23/15 by BiotechInvest
From PRAN MB
BiotechInvest: "My prediction about PRAN: pps $2 but after 1-for-4 reverse split, ongoing HD Ph3 with 250 mg daily PBT2 with Estimated Primary Completion Date 2018.
PRAN MB pumper kadaicher1: "My prediction as always on PRAN is PCH lifted and trial under way by year end. Parkinsons drug into trials first qtr 2016. No reverse split. Depending on how quick the HD trial is, the price could spike over $4. It has done that before on mouse results."
11/11/16 by BiotechInvestWell, it looks like that PRAN holders (and recent buyers at $6) again got huge losses. Current pps $2.46 ( 41 cents in before 1:6 RS price) is historically lowest. PRAN pumpers now play another card i.e. possible EMA submission and start Ph3 HD trial in Europe. As usually it's ugly lie. With cash $25M Prana CEO and management are not interesting in Ph3, they will just use this money to have 3-4 years of happy life. Then they will file a bankruptcy and say "goodbye" to stupid and stubborn PRAN holders. Will monitor this scam biotech to the end