Blarcamesine

Prions are the abnormal, pathogenic agents that are transmissible and are able to induce abnormal folding of specific normal cellular proteins. Prion disease is an umbrella term for a group of fatal and currently untreatable neurodegenerative diseases that not only affect humans, but also wild and captive animals. These diseases include Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE, or 'mad cow disease'), and chronic wasting disease (CWD) affecting deer, elk and moose. Prions are the abnormal, pathogenic agents that are transmissible and are able to induce abnormal folding of specific normal cellular proteins.Prion disease is an umbrella term for a group of fatal and currently untreatable neurodegenerative diseases that not only affect humans, but also wild and captive animals. These diseases include Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE, or "mad cow disease"), and chronic wasting disease (CWD) affecting deer, elk and moose. The central event in these diseases is the conversion of the prion protein (PrPC) from its normal shape into a pathological structure (PrPSc) that is toxic to neurons and can replicate itself through binding to unconverted PrPC molecules. This ability to self-replicate makes these misfolded proteins infectious, which has enormous implications for public health. In a new study, researchers from Boston University Chobanian & Avedisian School of Medicine have identified 10 compounds that are able to reduce PrPSc levels in infected cells and have shown that the most potent molecules can also prevent the toxicity that was observed when applying PrPSc to cultured neurons. "Excitingly, five of these molecules have a history of use in humans: rimcazole and haloperidol for neuropsychiatric conditions, (+)-pentazocine for neuropathic pain, and SA 4503 and ANAVEX2-73, which are in clinical trials for ischemic stroke and Alzheimer's disease, respectively," explained lead author Robert C.C. Mercer, PhD, an instructor of biochemistry and cell biology at the school. The researchers had initially explored the anti-prion properties of these molecules because they were known to bind to the sigma receptors (σ1R and σ2R), which they had reason to believe were involved in prion proliferation. Using gene knockout technology (CRISPR), they determined that the sigma receptors were not the relevant targets of these drugs, from the perspective of their anti-prion properties. Using Neuro2a cells (N2a) from an experimental model that had been infected with prions, these cells were then exposed to increasing concentrations of each drug, and the levels of PrPSc were determined. They then used CRISPR technology to "edit" the σ1R and σ2R genes, such that they no longer coded for a protein, and found this had no effect upon the decrease in PrPSc levels they observed when applying the drugs. This led them to conclude that σ1R and σ2R were not responsible for the anti-prion effects of these drugs. They then went on to test the ability of these drugs to inhibit the PrPC to PrPSc conversion and found they had no effect on these cell-free reactions, indicating that another protein mediates the effects of these drugs. According to the researchers, prion diseases have enormous public health implications from the safety of the blood supply to the proper decontamination of surgical tools used in neurosurgery. "From a clinical standpoint, we believe this research has uncovered anti-prion properties of drugs that have already been shown to be safe to use in humans. Because of this, especially considering the absence of any effective treatment for these diseases, these compounds could be re-purposed for treatment of prion diseases," said corresponding author David A. Harris, MD, PhD, the Edgar Minas Housepian professor and chair of biochemistry & cell biology at the school. These findings appear online in the journal ACS Chemical Neuroscience. Funding for this study was provided by the National Institutes of Health grant number 5R01NS065244, awarded to David A. Harris. Robert C.C. Mercer is supported by grants from the Department of Defense (W81XWH-21-1-0141) and the Creutzfeldt-Jakob Disease Foundation.

NEW YORK, May 13, 2024 /PRNewswire/ -- Levi & Korsinsky, LLP notifies investors in Anavex Life Sciences Corporation ("Anavex Life Sciences" or the "Company") (NASDAQ: AVXL) of a class action securities lawsuit. CLASS DEFINITION: The lawsuit seeks to recover losses on behalf of Anavex Life Sciences investors who were adversely affected by alleged securities fraud between June 21, 2021 and January 1, 2024. Follow the link below to get more information and be contacted by a member of our team: AVXL investors may also contact Joseph E. Levi, Esq. via email at [email protected] or by telephone at (212) 363-7500. CASE DETAILS: The complaint alleges that on December 2, 2022, AVXL announced positive topline results from its Phase 2b/3 ANAVEX®2-73-AD-004 clinical trial of oral ANAVEX®2-73 (blarcamesine) for the treatment of mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and mild AD (collectively known as early AD). ANAVEX®2-73 met the primary endpoints ADAS-Cog1 and ADCS-ADL2 and key secondary endpoint CDR-SB3 with statistically significant results. An analyst questioned the Company's claim noting "there are several key factors that point us to believe the data is provocative, but not yet compelling, given the choice of statistical analyses and other trial design/conduct 'complexifiers'." Additionally, a biotech journalist commented on AVXL's findings stating "[w]hat sets Anavex apart from all the other biotechs on my radar screen is its habit of shifting the goalposts on clinical trials…Anavex announced "positive" outcomes from studies of its drug called blarcamesine — except the results were derived from efficacy endpoints that were not part of the original study designs." Following this news, AVXL's stock price fell by $2.47 per share, or approximately 20% to close at $9.58. Further on January 3, 2024, AVXL announced that results from its Phase 2/3 EXCELLENCE clinical trial for its candidate ANAVEX®2-73 in pediatric patients with Rett syndrome failed to show statistical significance towards its primary endpoints. Biotech analysts commented that "the negative study outcome was never in doubt…Anavex is a serial dissembler of clinical trial results." Following this news, AVXL's stock price fell by $3.26 per share, or approximately 35%. WHAT'S NEXT? If you suffered a loss in Anavex Life Sciences during the relevant time frame, you have until May 13, 2024 to request that the Court appoint you as lead plaintiff. Your ability to share in any recovery doesn't require that you serve as a lead plaintiff. NO COST TO YOU: If you are a class member, you may be entitled to compensation without payment of any out-of-pocket costs or fees. There is no cost or obligation to participate. WHY LEVI & KORSINSKY: Over the past 20 years, the team at Levi & Korsinsky has secured hundreds of millions of dollars for aggrieved shareholders and built a track record of winning high-stakes cases. Our firm has extensive expertise representing investors in complex securities litigation and a team of over 70 employees to serve our clients. For seven years in a row, Levi & Korsinsky has ranked in ISS Securities Class Action Services' Top 50 Report as one of the top securities litigation firms in the United States. CONTACT: Levi & Korsinsky, LLP Joseph E. Levi, Esq. Ed Korsinsky, Esq. 33 Whitehall Street, 17th Floor New York, NY 10004 [email protected] Tel: (212) 363-7500 Fax: (212) 363-7171 SOURCE Levi & Korsinsky, LLP