Prana Biotech: PBT-2 - Die letzten 30 Beiträge
neuester Beitrag 19.11.15 09:15:17 von
Neuigkeiten zur Prana Biotechnology Aktie
I am writing this letter, first, to express my appreciation for your support of Prana Biotechnology and, more generally, drug development aimed at preventing and treating this terrible disease called Alzheimer’s disease (AD). Second, I would like to take the opportunity to update you on how recent studies modelling AD, using human stem cell-derived neurons grown in 3D cultures, have dramatically enhanced and clarified our understanding of the pathogenic events underlying AD-related neurodegeneration.
The past year of AD research has arguably been one of the most exciting in the last two decades. I say this in references to new revelations coming out of genetic studies of AD, as well as the insights regarding the etiology and pathogenic events underlying AD, emerging from our new model of the disease dubbed “Alzheimer’s-in-a-Dish”. We have developed this new model of AD using human stem cell-derived neural cultures grown in petri dishes in a gel that resembles the milieu of the brain. This is referred to as 3-D neural culture and we used it to recreate for the first time, the two major pathological hallmarks of AD - deposits of beta-amyloid protein, which appear as senile plaques (outside neurons), and twisted aggregates of tau proteins that manifest as neurofibrillary tangles (inside neurons). While those in the AD research field agree that it is the tangles and inflammation that kill neurons, heavy debate has raged for thirty years in the Alzheimer’s research community as to what initiates the tangles and deadly neurodegenerative cascade—the beta-amyloid or something else.
While our and other’s genetic studies of AD over the last three decades have strongly supported the notion that beta-amyloid acts as a trigger for tangle formation and neurodegeneration, evidence against this idea was suggested by two repeated findings. First, when the early-onset familial AD gene mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) were introduced into mice in attempts to create animal models for AD, plaques were observed, eventually leading to neuroinflammation, cell death, and cognitive deficits. However, no tangles were produced. This suggested beta-amyloid does not lead to tangles - at least, in mice. Second, many anti-amyloid therapies failed in clinical trials.
Now, Alzheimer’s-in-a-dish, using human (not mouse) neurons, has clearly shown that beta-amyloid is sufficient to lead directly to tangles (after ~9 weeks in culture). Furthermore, we showed that if you stop the deposition of beta-amyloid, you also stop the tangles. Regarding the numerous failed clinical trials targeting beta-amyloid, we now know that beta-amyloid accumulates 10-20 years before any cognitive symptoms of AD and that treating AD by only targeting amyloid in mid-late stage patients is too little-too late. Beta-amyloid deposition must be targeted as early as possible, preferably at the pre-dementia stage of the disease process.
Recent discoveries in AD genetics have also strongly implicated neuroinflammation as the third pillar of AD pathology (in addition to beta-amyloid deposition (e.g. as senile plaques and neurofibrillary tangles). In 2008, we discovered the new AD gene, CD33, and in 2012, Decode (Iceland) discovered the AD gene, TREM2. We now know that these two genes play a major role in controlling neuroinflammation in AD. These are now serving as drug targets for regulating neuroinflammation in AD. This is particularly important in patients with mid-late stage AD.
The newest combined genetic, imaging, biomarker, and Alzheimer’s-in-a-Dish data now collectively illustrate a path for Alzheimer’s pathology in which first, beta-amyloid accumulates in the brain, decades before cognitive impairment. Beta-amyloid then triggers the production of tangles that kill neurons from within as well as neuro-inflammation, which kills more neurons. As increasing numbers of neurons die, there is more neuro-inflammation driven by microglial cells (regulated by the genes, CD33 and TREM2). Inflammation then drives even more plaques and tangles, and a vicious cycle ensues.
We have been using Alzheimer’s-in-a-Dish to find drugs that will slow or halt plaque and tangle formation. Among those that are being tested is PBT2. Studies of PBT2 are still in progress and once confirmed, will be submitted for publication. So far, the preliminary findings show that 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. Once these results are confirmed, PBT2 would become the only compound tested in Alzheimer’s-in-a-Dish to achieve all three of these effects on AD pathology.
In closing, based on recent findings, I firmly believe, that beta-amyloid remains the best target for preventing and treating AD, but this must be achieved in the earliest stages of the disease process. Based on the combined data, I continue to believe that PBT2 carries great potential for curbing plaque and tangle formation, while also enhancing neuronal cell viability as an AD therapeutic.
Rudolph E. Tanzi, Ph.D.
Wenn man das US Board liest könnte es hier abgehen. Bin ich gespannt mit meinem Long Investment.
Nur meine Meinung, keine Kauf- oder Verkaufsempfehlung.
mal gut das mit 0,22 € der einstiegskurs nun nicht ganz so doll schmerzt.
also kaufen schlafengehen und 10 jahre später mal schaun lol
Dr. Rudy Tanzi @RudyTanzi (vor 3 Std.)
PBT2 misses primary endpoint in study of 40 Alzheimer's patients, but continues to be developed for Alzheimer's and Huntington's disease.
Code: PBT - PRANA BIOTECHNOLOGY LIMITED
"Let's not spin it. The result is a shock, the trial failed. Let's not spin it because the people who got it right for all the wrong reasons appear to have won. Let's not spin it because we have lost our money or our profits.
Let's be sad for the people with, and the carers of people with, degenerative neurological conditions who have had their short term hopes for a genuine modifier of these conditions dashed.
Hopefully, it is not the end of PBT2 as a potential treatment, but the road ahead is now longer and harder. Let's hope that the curse of AD and other neurological conditions, has suffered an irrecoverable dent from the efforts of the scientists and believers involved in this project. Let's hope that this unexpected setback is not the end, but another beginning in the fight for an effective treatment.
Most of all let's hope that these results are analysed objectively. It is no good flogging a dead horse, but neither is it prudent to throw out the baby with the bath water.
It has been a pleasure to read and contribute to this forum. Good luck to all those who gave their time and researched fairly and objectively over the years - there is no blame there.
This result is the nature of the scientific method which, hopefully, will prevail in the end."
Prana says drug fails Alzheimer's disease study
Prana Biotechnology's (ASX: PBT, NASDAQ: PRAN) shares are in pre-open today, following the ASX granting the company a trading halt.
The halt was granted pending results of its PBT2 IMAGINE Alzheimer’s Disease Phase II Trial.
PBT's shares last traded at around $1, which is five times higher than a year ago.
The halt will remain in place until the opening of trade on Wednesday 2nd April 2014, or earlier if an announcement was made to the market.
Bislang sind alle Versuche gescheitert, Alzheimer zu heilen. Es kann sein, dass sie in die falsche Richtung gingen.
Course of Sales 21.03.2014
Time (AEST) Price Volume Value
18:47:01 1.239 416,552 516,107.93
18:46:50 1.239 41,964 51,993.40
18:46:35 1.239 115,545 143,160.26
18:34:15 1.239 998,592 1,237,255.49
18:04:30 1.240 294,210 364,820.40
A very curious trade:
18:03:08 3.718 574,06 2,134,358.80
17:00:23 1.239 2,334,225 2,892,104.78 -> after hours
16:10:44 1,2400 7.927.000 -> Schlusskurs
15:59:39 1,2000 9
March 20, 2014
superpisboy • 4 hours ago
Fidelity The biggest Mutual Fund Holder in Prana and ICPT
Fidelity has almost the same amount of shares in PRana as it does in ICPT, and in my opinion the Prana investment could surpass ICPT.
Who Wins With Intercept?
By Brendan Conway
"The remarkable surge in Intercept Pharmaceuticals’ (ICPT) stock — 582% this year, at last check — appears to have delivered handy gains to some well-known Fidelity Investments mutual funds. But it may have just missed one of the firm’s most famous funds.
The big winner appears to be Fidelity Select Biotechnology (FBIOX). This mutual fund owned a little over 1.31 million shares as of the end of November, a position valued at $68.9 million... "
PRAN wird in Kürze in den ASX 300 aufgenommen:
Prana Biotechnology (PRAN) is set to join the S&P/ASX 300 Index on March 21 following a quarterly review by Dow Jones.
The S&P/ASX 300 is adjusted every quarter to reflect Australia's largest 300 companies by market cap. Dow Jone's decision comes after Prana's valuation surged to over $415M.
Entrance to the S&P/ASX 300 will expose Prana to a wider range of investors.
Fidelity bought 1m Prana shares
Wikipedia: Fidelity Investments
"Die FMR LLC (Fidelity Investments), häufig kurz Fidelity, ist ein US-amerikanisches Unternehmen der Finanzdienstleistungsbranche mit Stammsitz in Boston, Massachusetts. Das Unternehmen ist einer der größten Vermögensverwalter der Welt..."
im März kommen die P-II Alzheimer Ergebnisse - ein binärer Event für Prana!
March 07, 2014
Alzheimer's Research Stocks - Technical And Other Considerations
Source: George S. Mack of The Life Sciences Report (3/6/14)
George Zavoico Prospecting for hidden biotech gems makes sense, says H.C. Wainwright & Co. Managing Director George Zavoico, who recently joined the firm's healthcare equity research team. The digging can be hard, but the rewards of successful diligence are huge. In this interview with The Life Sciences Report, Zavoico takes readers on a discovery tour that follows clinical trial data to new ideas that could bring windfalls to portfolios down the road.
The Life Sciences Report: What theme do you see working for investors in 2014?
TLSR: Could you talk about Prana Biotechnology Ltd. (PBT:ASX), which you've just initiated on?
GZ: Certainly. Prana has a compound called PBT2 in clinical trials. On Feb. 18, the company announced results of its phase 2a trial in Huntington's disease (HD). The primary endpoint in this randomized, double-blind study was the safety and tolerability of PBT2 in patients with HD. The exact primary endpoint was the frequency of adverse events over 26 weeks, and it turned out that the compound met that endpoint. This was not surprising, because the drug had been safely administered to Alzheimer's disease (AD) patients in a previous phase 2a trial.
Here's where things get interesting. I cautioned investors not to overinterpret and expect statistically significant data on efficacy from phase 2 trials at the start of this interview. This trial, called Reach2HD, was first and foremost a phase 2a safety trial, since PBT2 had never before been given to HD patients. A panel of secondary endpoints—a long list actually—were examined with no expectation of finding statistically significant efficacy results. Recall what I said earlier about looking for trends, not statistical significance. Prana was looking for trends in cognitive function that could then be fashioned into a confirmatory phase 2b trial that would increase the likelihood of showing a clinically significant benefit—a meaningful improvement in cognitive function.
A surprising thing was discovered in this phase 2a trial. One of the cognitive measures, specifically the Trail Making Test Part B, demonstrated a statistically significant improvement in performance versus placebo at both 12 and 26 weeks. This test is an assessment of executive function—a patient's capacity to plan and organize things and to multitask, which is weakened early on in both HD and AD. The same cognitive function showed a statistically significant improvement with PBT2 in an earlier, phase 2a AD trial, and it is also a secondary endpoint in an ongoing AD trial that's going to read out before the end of March, according to the company's guidance. If this same secondary endpoint is met in the phase 2b trial, that would be confidence building, to say the least.
TLSR: The results of the high dose of 250 mg versus the low dose of 100 mg are delineated in the phase 2a PBT2 trail. Is the efficacy of the high-dose arm strong compared to the low-dose arm?
GZ: That's right. Also, in that regard, a very small substudy was performed, in which the brains of four patients in both PBT2 trial arms were imaged. Just as in Alzheimer's disease, the brain shrinks in Huntington's disease. There was some evidence that brain atrophy was reduced in the HD patients taking PBT2. Understand that this was a trend toward conservation of brain volume with PBT2, and was not statistically significant because of the small patient population. But it was an exciting result, nevertheless.
TLSR: What is it about PBT2 that makes it potentially efficacious in Alzheimer's and Huntington's diseases?
GZ: The common pathogenesis of these diseases is protein misfolding. The misfolding is facilitated and enhanced by metals—zinc and copper, in particular. The physiologic mechanisms that remove zinc and copper, which are released and exist very transiently in the synapse during neurotransmission, just don't work as well as we age. In younger people, the metals are immediately bound and transported back to their intracellular storage sites. If they stay longer in the synapse—that space between nerve cells—they can interact with those proteins and aggregate. As disease progresses, these metal-binding proteins, or metalloproteins, form plaques, which cause dysfunction in neurotransmission and ultimately an inflammatory response that kills the affected and surrounding neurons. That's when patients begin to get overt symptoms.
In Alzheimer's and Huntington's diseases, the misfolded proteins are beta-amyloid and mutant huntingtin protein, respectively. PBT2 has a chaperone-type activity that appears to strip zinc and copper from these metalloproteins, then transports them across the neuronal cell membrane and delivers them to intracellular proteins, where the metals are normally stored. In animal models, PBT2 has been shown to reduce the amyloid burden in the brain, meaning that the amount of amyloid plaques is reduced. This is the primary endpoint in the ongoing Alzheimer's disease trial, called IMAGINE, that is expected to read out before the end of March.
Here's where it may get very exciting. If PBT2 reduces the amyloid burden in Alzheimer's disease patients after a year of treatment, and improves cognitive function, then it will be the only drug candidate to have shown this. In our view, the risk-reward ratio for PBT2 is tremendous.
Let me just caution readers that PBT2 may also fail to show a reduction in amyloid burden, in which case we expect Prana's stock to take a big hit. But having reviewed the preclinical and early clinical results to date, we think this trial has a better chance of succeeding than failing.
djnato2007 • 10 minutes ago
Adam F has bacically cost me $15000 in 1 month
He and the Stinking Alpha guys basically made me fail, along with my lack of understanding of the Short bash trickery and being a fearful idiot. Good luck to all you rich guys that can handle the swings. Just another failure for me. Thanks Adam F and the stinking alpha scam.