HANUMAN
4月前
A study shows that rising levels of brain protein Aß42, not the reduction of amyloid plaques, better explains the cognitive benefits of new Alzheimer’s drugs. This finding challenges the traditional focus on plaques in Alzheimer’s treatment.
A new study reveals that the rise in protein levels due to new Alzheimer’s drugs may explain the slowing of cognitive decline just as effectively as the reduction of amyloid plaques.
In a study that questions the effectiveness of newly approved monoclonal antibodies in reducing cognitive decline in Alzheimer’s patients by clearing amyloid, researchers from the University of Cincinnati discovered that an unintended rise in a critical brain protein’s levels correlates just as strongly with cognitive benefits.
Led by UC’s Alberto Espay, MD, the research was published in the journal Brain.
Study background
For decades, the prevailing theory in the field has stated that a protein made up of 42 amino acids called amyloid-beta 42 (Aß42) hardens into clumps called amyloid plaques, and those plaques damage the brain, causing Alzheimer’s disease.
Espay and team have hypothesized that normal, soluble Aß42 in the brain is crucial for neuron health and that the loss of Aß42, rather than the buildup of plaques, drives Alzheimer’s. This includes published research that suggests dementia occurs not when plaque levels are high but when Aß42 levels drop very low.
According to Espay’s research, the transformation of Aß42 into plaques appears to be the brain’s normal response to biological, metabolic, or infectious stress.
Alberto Espay
Alberto Espay, MD, MSc, professor of neurology at the UC College of Medicine and Director and Endowed Chair of the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders. Credit: Colleen Kelley/UC Brand + Creative
“Most of us will accrue amyloid plaques in our brains as we age, and yet very few of us with plaques go on to develop dementia,” said Espay, professor of neurology in the UC College of Medicine and director and endowed chair of the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders at the UC Gardner Neuroscience Institute. “Yet the plaques remain the center of our attention in biomarker development and therapeutic strategies.”
Study details
Recently, several new monoclonal antibody medications designed to remove amyloid from the brain were approved after showing they lessened cognitive decline in clinical trials.
Espay and his colleagues noticed that these drugs unintentionally increased levels of Aß42.
“Amyloid plaques don’t cause Alzheimer’s, but if the brain makes too much of it while defending against infections, toxins, or biological changes, it can’t produce enough Aß42, causing its levels to drop below a critical threshold,” Espay explained. “That’s when dementia symptoms emerge.”
The team analyzed data from nearly 26,000 patients enrolled in 24 randomized clinical trials of these new antibody treatments, assessing cognitive impairment and differences in levels of Aß42 before and after treatment. They found that higher levels of Aß42 after treatment were independently associated with slower cognitive impairment and clinical decline.
“All stories have two sides — even the one we have told ourselves about how anti-amyloid treatments work: by lowering amyloid,” Espay said. “In fact, they also raise the levels of Aß42. Even if this is unintended, it is why there may be a benefit. Our study shows that we can predict changes in cognitive outcomes in anti-amyloid trials at least as well by the increases in Aß42 as by the decreases in amyloid.”
Espay said these findings fit well into his larger hypothesis about the root cause of Alzheimer’s, as increasing levels of Aß42 appear to improve cognition.
“If the problem with Alzheimer’s is the loss of the normal protein, then increasing it should be beneficial, and this study showed that it is,” he said. “The story makes sense: Increasing Aß42 levels to within the normal range is desirable.”
However, Espay believes these results also present a conundrum for clinicians because removing amyloid from the brain is toxic and may cause the brain to shrink faster after antibody treatment.
“Do we give patients an anti-protein treatment to increase their protein levels? I think the end, increasing Aß42, doesn’t justify the means, decreasing amyloid,” Espay said. Therapies that directly increase Aß42 levels without targeting amyloid are a focus of research for Espay and his group
XenaLives
9月前
This shell was a trading vehicle, bryostatin failed multiple times. Insiders knew this. It's all linked in my sticky.
Executive Summary:
Neurotrope was created in a reverse merger in August 2013 by Adam Gottbetter and Michael Silverman. The Neurotrope promotion was delayed when Gottbetter was sent to prison for stock fraud in early 2015.
Gottbetter was released from prison in November 2016. Exactly ONE DAY LATER, NTRP raised approx. $25 million in a stock sale, run by Gottbetter's former partner Michael Silverman. NTRP price and volume took off ( nearly tripled in the following 100 days). The stock is now collapsing.
Gottbetter's former partner, Michael Silverman, was barred by FINRA after forging customer signatures ( link). He was also arrested and indicted as part of an illegal gambling ring run by the Luchese mafia crime family ( link).
NTRP's "drug" (bryostatin) has been evaluated for more than 48 years against AIDS, cancer and now Alzheimer's. Simply put: it always failed. Documents show that Blanchette Rockefeller Institute actually filed for bankruptcy on July 28, 2016 ( Link 1). BRNI was running the research on Bryostatin.
Just weeks after the BRNI bankruptcy filing, hedge fund manager Joshua Silverman supposedly left his fund Iroquois Capital to become Chairman of Neurotrope. Joshua Silverman and Iroquois are currently under SEC investigation for their role in an imploded stock promotion called MGT Capital which appears to be very similar to the Neurotrope promotion. Although Silverman says he left Iroquois, suddenly Neurotrope began using the same address as Iroquois.
Various parties involved in Neurotrope are using multiple arrangements to drain much of the cash from Neurotrope IMMEDIATELY after capital raises. They are making millions of dollars without any need for any successful drug - EVER.
Stock promoters behind Neurotrope are using alternate identities, but trace back to a New York IR firm called JV Public Relations NY which is linked to Neurotrope. Janet Vasquez, who runs JV Public Relations, was formerly the PR rep for Forcefield Energy (SunSi Energy), which was delisted due to fraud as its Chairman was arrested.
Below I will show that Sharon Di Stefano has written more than a dozen articles using the name "Small Cap Forecasting" or "SCF". But the phone number tied to SCF articles distributed though ACCESSWIRE actually belongs to JV Public Relations At least 10 (out of 15) of the companies covered by Di Stefano also happen to be tied to JV Public relations. All 10 of those stocks are also featured on an additional biotech stock promotion site which does not disclose compensation. THIS INCLUDES NEUROTROPE. INCIDENTALLY, IT ALSO INCLUDES TAPIMMUNE (TPIV).
Just like NTRP, Tapimmune is another stock where Joshua Silverman's Iroquois Capital holds 9.99%. Just like NTRP, Tapimmune received bullish coverage from Di Stefano. Just like NTRP, Di Stefano's bullish article was then disseminated by a paid press release tied to JV Public Relations. Just like NTRP, Tapimmune also used Michael Silverman's Katalyst Securities to raise money.
Despite the information contained in this report, Sharon Di Stefano claims that she doesn't know who Janet Vasquez or Jackie Rodriguez work for ( link). Truth is, they run JV Public Relations NY, the microcap IR firm in New York. The phone number listed as "media contact" for Di Stefano's Small Cap Forecasting happens to be the same as of JV Public Relations. Neurotrope has already come out with a public statement denying at it is not involved in any paid promotion behind its stock. Who is paying JV Public Relations NY?
My prior sticky is also linked, posted in August of 2020, this is the summary, historic quotes and evidence follow:
Neurotrope is a front for old money and connected folk. They are trying to commercialize a very OLD drug that has not been taken forward because it needs to be synthesized as the natural version is too rare. Most, if not all of the research on this drug has been paid for by the U.S. government.
Three years ago I stated my discomfort with the way this company came into being and was run:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=128690545
Shortly after this was posted the Pump and Dump I prophesied was realized and a great deal of retail money was taken out of the U.S. market, minimizing the risk of the founding stockholders.
Retail will continue to get the short end of the stick here to the bitter end. I will not invest in this company because I know how it ends... If the science is not successful the company goes broke and retail will be the bagholder. If it is successful read to the end of this post to find the outcome.
This drug is owned by old money "non profit" institutions. These are the two most prominent in the story:
Rockefeller Neuroscience Institute
https://directory.hsc.wvu.edu/Department/2192
Woods Hole Oceanographic Institution
www.whoi.edu
The initial investors have been selling stock to recoup their initial cost of funding the company on price spikes and replenishing it with warrants.
I am not convinced that treating Alzheimer's is the primary goal of Neurotrope. It is also not clear that people who buy stock in NTRP will be the primary beneficiaries if the company is successful. I suspect it will be the founding stockholders who have probably already made most of their "investment" back by selling at higher prices.
I am also not sure if there is solid protection for the IP as with proof of concept someone might design a new synthetic chemical that could do it all better. They have patents but I don't know how enforceable they would be against a newly designed chemical.
This paragraph is updated from the previous sticky:
I think Anavex may draw the ire of NTRP proponents because 2-73 creates cellular homeostasis which is both neuroprotective and allows neurogenesis to take place. Blarcamesine or 2-73 is in trials for Alzheimer's, Parkinson's dementia, and is both neuroprotective and restorative. It is more economical than bryostatin could ever be and may get provisional approval from the Australian TGA within a year.
... and then there's 3-71.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=157967774
XenaLives
12月前
The replied to post contains my old sticky on this scam...
The racket is still the same...
XenaLives
Member Level
Re: None
Sunday, March 24, 2019 10:43:29 AM
Post# 8938 of 21500
Neurotrope is a front for old money and connected folk. They are trying to commercialize a very OLD drug that has not been taken forward because it needs to be synthesized as the natural version is too rare. Most, if not all of the research on this drug has been paid for by the U.S. government.
Two years ago I stated my discomfort with the way this company came into being and was run:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=128690545
Shortly after this was posted the Pump and Dump I prophesied was realized and a great deal of retail money was taken out of the U.S. market, minimizing the risk of the founding stockholders.
Retail will continue to get the short end of the stick here to the bitter end. I will not invest in this company because I know how it ends... If the science is not successful the company goes broke and retail will be the bagholder. If it is successful read to the end of this post to find the outcome.
This drug is owned by old money "non profit" institutions. These are the two most prominent in the story:
Rockefeller Neuroscience Institute
https://directory.hsc.wvu.edu/Department/2192
Woods Hole Oceanographic Institution
www.whoi.edu
The initial investors have been selling stock to recoup their initial cost of funding the company on price spikes and replenishing it with warrants.
I am not convinced that treating Alzheimer's is the primary goal of Neurotrope. It is also not clear that people who buy stock in NTRP will be the primary beneficiaries if the company is successful. I suspect it will be the founding stockholders who have probably already made most of their "investment" back by selling at higher prices.
I am also not sure if there is solid protection for the IP as with proof of concept someone might design a new synthetic chemical that could do it all better. They have patents but I don't know how enforceable they would be against a newly designed chemical.
I think Anavex may draw the ire of NTRP proponents because 2-73 achieves the same goal of neurogenesis with a chemical that clearly does not fall under their IP umbrella. I also believe we will be on the market sooner with a drug that is much more economical than theirs making their franchise worthless....
... and then there's 3-71.
This is how it plays out historically:
OLD NEWS - on Bryostatin and Cancer:
Source: DGNews | Posted 17 years ago
FDA Grants Orphan Drug Designation To Bryostatin-1, In Combination With Taxol (Paclitaxel), For Esophageal Cancer
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MARTINSRIED/MUNICH, GERMANY and WALTHAM/BOSTON, MA -- December 12, 2001 -- GPC Biotech AG, a leading genomics- and proteomics-driven drug discovery and development company, announced that the United States Food and Drug Administration (FDA) has granted Orphan Drug Designation for its Phase II clinical compound Bryostatin-1 in combination with Taxol (paclitaxel) for the treatment of esophageal cancer.
The orphan drug designation allows GPC Biotech exclusive marketing rights for the esophageal cancer indication in the US on Bryostatin-1 for seven years following marketing approval by the FDA. The designation also enables GPC Biotech to apply for research funding, tax credits on certain research expenses and a waiver from the FDA's application user fee.
Preliminary results from a current Phase II study at Memorial Sloan Kettering Cancer Center suggest that Bryostatin-1 increases tumor response when used in combination with Taxol against esophageal cancer.
GPC Biotech plans to advance Bryostatin-1 through Phase III clinical studies in combination with Taxol for the treatment of esophageal cancer as well as other clinical trials in additional indications if the clinical results continue to be positive.
In addition to the clinical trials for esophageal cancer, Bryostatin-1 is currently in a number of additional Phase II human clinical trials in combination with other therapeutics for several different indications.
Bryostatin-1 is linked to the modulation of Protein Kinase C (PKC), a well-validated anti-cancer target. PKC is an attractive target for cancer chemotherapy as this kinase family plays a fundamental role in the development of cancer through regulating cell growth and programmed cell death (apoptosis).
Esophageal cancer is a devastating disease with a tremendous unmet medical need. The FDA's orphan drug designation is intended to encourage research and development of new therapies for diseases that affect fewer than 200,000 US residents.
SOURCE: GPC Biotech AG
https://www.docguide.com/fda-grants-orphan-drug-designation-bryostatin-1-combination-taxol-paclitaxel-esophageal-cancer
Bryostatin 1 Induces Biphasic Activation of Protein Kinase D in Intact Cells*
Sharon A. Matthews‡, George R. Pettit§ and Enrique Rozengurt‡¶
+ Author Affiliations
From the ‡Growth Regulation Laboratory, Imperial Cancer Research Fund, 44 Lincoln’s Inn Fields, London WC2A?3PX, United Kingdom, and the §Cancer Research Institute and Department of Chemistry, Arizona State University, Tempe,?Arizona?85287
Next Section
Abstract
Bryostatin 1 and phorbol esters are both potent activators of protein kinase C (PKC), although their specific biological effects can differ in many systems. Here, we report that bryostatin 1 activates protein kinase D (PKD), a novel serine/threonine protein kinase, in intact Swiss 3T3 cells and secondary mouse embryo fibroblasts and in COS-7 cells transiently transfected with a PKD expression construct. The dose response of PKD activation induced by bryostatin 1 follows a striking biphasic pattern with maximal activation achieved at a concentration of 10 nM. Higher concentrations of bryostatin 1 (100 nM) reduced PKD activation induced by phorbol 12,13-dibutyrate to levels stimulated by bryostatin 1 alone. Bryostatin 1-induced PKD activation was markedly attenuated by treatment of cells with the PKC inhibitors bisindolylmaleimide I and Ro 31-8220. However, these agents did not inhibit PKD activity when added directly to in vitro kinase assays, suggesting that bryostatin 1 stimulates PKD activation through a PKC-dependent pathway in intact cells. Our results raise the possibility that activated PKD in intact cells could mediate some of the multiple biphasic biological responses induced by bryostatin 1.
Bryostatin 1 is a natural macrocyclic lactone with potent antineoplastic properties in a variety of animal models (1-3) and has entered clinical trials as a potential therapeutic agent (4, 5). Bryostatin family members bind to and activate classic and novel isoforms of protein kinase C (PKC)1 (6-9), the major cellular targets of the tumor-promoting phorbol esters (10). Despite appearing to bind to the same cellular targets, the biological responses induced by bryostatin 1 frequently differ from those induced by phorbol esters. For example, many bryostatin 1-mediated effects have unusual characteristics such as biphasic dose-response relationships, delayed kinetics, and the ability to inhibit phorbol ester-induced responses (7, 11-16). The precise mechanism(s) by which bryostatin 1 induces these biological effects remain poorly understood.
The newly identified protein kinase D (PKD) is a mouse serine/threonine protein kinase with distinct structural features and enzymological properties (17-19). In particular, the catalytic domain of PKD, which is distantly related to Ca2+-regulated kinases, shows little homology to the highly conserved regions of the kinase domain of the PKC family. As a consequence of this, PKD does not phosphorylate a variety of known PKC substrates, indicating that PKD has a distinct substrate specificity (18, 19).
The amino-terminal region of PKD contains a putative transmembrane domain, two cysteine-rich zinc finger-like motifs, and a pleckstrin homology domain. Unlike all known PKC isoforms, PKD does not contain a pseudosubstrate motif upstream of the cysteine-rich region, and the sequence separating the cysteine-rich repeats of PKD (95 amino acids) is substantially longer than that of classical and novel PKCs (28 and 35 amino acids, respectively). Additionally, residues Ala-146, Ala-154, and Tyr-182 in the consensus cysteine-rich motif of PKD differ from those found in PKCs. However, both immunopurified PKD and a fusion protein containing the cysteine-rich region of PKD bind phorbol esters with high affinity, and PKD is directly stimulated in vitroby these agents, or by diacylglycerol, in the presence of phospholipids (18, 19). A human protein kinase called atypical PKCµ (20) with 92% homology to PKD is also stimulated in vitro by phorbol esters and phospholipids (21). These results indicate that PKD/PKCµ are phorbol ester/diacylglycerol-stimulated protein kinases. Recent studies have demonstrated a novel mechanism of activation of PKD. Specifically, treatment of intact cells with biologically active phorbol esters induces phosphorylation-dependent activation of PKD through a PKC-dependent pathway (22). PKD activity recovered from phorbol ester-stimulated cells can be measured by kinase assays in the absence of lipid activators. These results revealed an unsuspected connection between PKCs and PKD and suggested that PKD can function parallel to and/or downstream of PKC in signal transduction pathways.
The differences between the biological effects elicited by phorbol esters and bryostatin 1 in certain systems prompted us to examine whether bryostatin 1 regulates PKD activity in intact cells. Here we report that treatment with bryostatin 1 induces PKD activation in intact Swiss 3T3 cells and MEF and in COS-7 cells transfected with a PKD expression vector. A salient feature of our results is that bryostatin 1-mediated activation of PKD follows a striking biphasic dose-response relationship. PKD activation induced by treatment with PDB was inhibited by high concentrations of bryostatin 1. These results raise the possibility that PKD could mediate some of the multiple biological responses induced by bryostatin 1.
http://www.jbc.org/content/272/32/20245.full
GPC Biotech AG
GPC Biotech logo orange.png
Type Public
Founded August 1997
Location Martinsried, Germany
Key people Bernd R. Seizinger, M.D., Ph. D. (CEO)
Mirko Scherer, Ph. D. (CFO)
Industry Biotechnology
Products 3 in Clinical or Pre-clinical development
Revenue €12,649 (2004)
Website www.gpc-biotech.com/
GPC Biotech (also referred to as GPCbiotech and GPC-Biotech) was a German biopharmaceutical company. The company's mission statement reads "... to discover, develop and commercialize new anticancer drugs."[1]
Founded in 1997, the company was held privately until May 2000 when an initial public offering was made on the now defunct German Neuer Markt. Subsequent to the closing of the Neuer, GPC refinanced in June 2004 through a public stock offering and listed ADRs on NASDAQ.
In March 2000, the company acquired Mitotix, a United States biotechnology firm located in Cambridge, Massachusetts. This acquisition has led to the company having ~50% of its employees based in the United States and the remaining 50% in Germany. Further, the acquisition of Mitotix provided convenient proximity to GPC's long term and continuing collaboration with ALTANA Pharma AG and the ALTANA Research Institute, located in Waltham, Massachusetts.
In November 2009, Agennix AG acquired GPC Biotech [2].
In 2013 Agennix AG went into liquidation.
https://en.wikipedia.org/wiki/GPC_Biotech
About Altana - and how retail got screwed...
Altana's roots go back to 1873, when Heinrich Byk founded the chemicals factory Dr. Heinrich Byk Chemische Fabrik in Oranienburg. The company grew, and in 1931 it was renamed BYK-Gulden Lomberg. In 1941 majority control of the company was acquired by AFA (Akkumulatoren-Fabrik AG) which was renamed VARTA in 1962. In 1977 VARTA was split into three companies, one of which was Altana.[7]
From 1977 to 2010, Altana was publicly traded on the Frankfurt Stock Exchange. Altana was also admitted to trading on the New York Stock Exchange from 2002 to 2007.
On December 19, 2006 the majority of shareholders voted to approve the sale of the pharmaceuticals division to the Danish company Nycomed. Nycomed is owned by an investment consortium led by Nordic Capital and Credit Suisse. With the sale of the pharmaceuticals division, headquartered in Konstanz, Germany, Altana lost a major pillar of its business. At that time, 9,000 of the company’s 13,500 employees were working for Altana in the pharmaceuticals sector, generating two-thirds of the company’s total revenue. And indeed, the balance-sheet revenues fell by around 60 percent in 2006, but gained over six percent in 2007.
The patent for pantaprazole, the main revenue-generator for the former pharmaceuticals division, expired in 2009/2010. While the Altana Management Board justified the divestiture of the pharmaceutical business with delays in the approval of new products, increased research and development costs as well as strict regulatory requirements in the US and Europe, shareholder activists asserted that the Management Board had invested too little in the pharmaceutical business in the preceding years and had failed to develop successor products in time to compensate for the revenue losses to be expected due to the expiry of the pantaprazole patent at the end of the decade.
The pharmaceuticals division was sold for €4.6 billion. The entire proceeds from the sale were disbursed to the shareholders, who received a special dividend of €33 per share. Critics expressed discontent that the main shareholder benefited most from the sale of the pharmaceuticals division.
Until January 1, 2007, the company was organized into the pharmaceuticals division Altana Pharma AG, formerly Byk Gulden Lomberg Chemische Fabrik, headquartered in Konstanz, and the specialty chemicals division Altana Chemie AG based in Wesel. Since the sale of the pharmaceutical business to Nycomed, Altana has been operating exclusively in the specialty chemicals segment. This restructuring was accompanied by a change in the company logo, which was unified across all subsidiaries.
On November 6, 2008, main shareholder SKion GmbH (Germany, owned by Susanne Klatten) issued a public takeover offer of €13 per share for all outstanding shares, an action which drove up the stock price. A company spokesperson stated that the intention was to delist the company from public trading. To achieve this, SKion issued a second takeover offer of €14 per share to the remaining shareholders on November 9, 2009.
On December 30, 2008, the Frankfurt Stock Exchange announced that Altana would be removed from its MDAX index, as the increase in the share held by SKion had pushed the portion of stock held in free float to under ten percent. By June 2010, SKion held 95.04 percent of all shares.
In Germany, the stock was traded mainly on the Frankfurt and Stuttgart Exchanges and the Xetra platform; internationally, it was admitted to trading on the London Stock Exchange and the NASD Group, now FINRA, in the US.
After SKion acquired the entire Altana stock through a squeeze-out, trading in this stock was suspended effective August 27, 2010.
https://en.wikipedia.org/wiki/Altana
Susanne Klatten
From Wikipedia, the free encyclopedia
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Susanne Klatten
2017-09-12 IAA 2017 Susanne Klatten bei BMW by Olaf Kosinsky-10.jpg
Born Susanne Hanna Ursula Quandt
28 April 1962 (age 56)
Bad Homburg, Germany
Residence Bad Homburg[1]
Citizenship Germany[1]
Education IMD-Lausanne (MBA)
Known for holdings in Altana and BMW; richest woman in Germany
Net worth US$25.1 billion (March 2018)[1]
Spouse(s) Jan Klatten (m. 1990)
Children 3 [1]
Parent(s) Herbert Quandt (1910–1982)
Johanna Quandt (1926–2015)
Relatives Stefan Quandt (brother; b. 1966)
Susanne Klatten (born Susanne Hanna Ursula Quandt on 28 April 1962) is a German heiress, the daughter of Herbert and Johanna Quandt. As of March 2018, her net worth was US$25.1 billion, making her the richest woman in Germany and the 38th richest person in the world.[2]
https://en.wikipedia.org/wiki/Susanne_Klatten
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