Encephalopathy, Bovine Spongiform

MONDAY, Jan. 29, 2024 -- Five of eight British children who received human growth hormone from the pituitary glands of deceased donors went on to develop early-onset Alzheimer's disease many decades later, researchers report. Researchers at University College London (UCL) suspect that the growth hormone received by these people in childhood may have contained amyloid-beta protein plaques, which build up in the brains of people with Alzheimer's disease over time. Their finding suggests that -- in very rare contexts like these -- the brain-robbing disease could be transmitted person-to-person. However, "there is no evidence that amyloid beta can be transmitted in other contexts -- for example, during activities of daily life or provision of routine care," wrote a team led by Dr. John Collinge . He's a professor of neurology and head of the department of neurodegenerative disease at the UCL Institute of Neurology. The findings were published Jan. 29 in the journal Nature Medicine . As explained by the researchers, between 1959 and 1985 British children with growth issues were sometimes treated with human growth hormone that was extracted from the pituitary glands of cadavers. However, doctors worldwide put a halt to the practice when it came to light that these procedures could transmit a type of misfolded protein called a prion, which in turn could trigger a deadly degenerative brain disorder called Creutzfeldt–Jakob disease (CJD). When seen in animals, the illness is nicknamed "mad cow disease." Autopsies conducted by Collinge's team showed that some patients who'd died of CJD in this way also showed signs of Alzheimer's amyloid-beta buildup. Other studies conducted by the same team showed that cadaver-sourced growth hormone stored in labs did, in fact, contain amyloid-beta. When these hormone samples were injected into mice, the rodents went on to develop a pathological buildup of amyloid-beta in their brains. All of this spurred Collinge's team to track the brain health histories of eight Brits who had received cadaver-sourced hormone as kids, but who were spared CJD. Five of the eight people went on to develop early-onset Alzheimer's disease, defined as onset of symptoms between the age of 38 and 55, the researchers found. These people had dementia symptoms severe enough to impair daily living, Collinge's team reported. Of the remaining three individuals, one developed symptoms of mild cognitive impairment (often a precursor to Alzheimer's) by the age of 42, another showed non-definitive "subjective" cognitive symptoms, while the other showed no signs of cognitive impairment, the study found. Five of the patients underwent genetic testing which ruled out the possibility that any of them had an inherited form of early-onset Alzheimer's. All of this suggests "that Alzheimer's and some other neurological conditions [can] share similar disease processes to CJD," Collinge said in a UCL news release. "This may have important implications for understanding and treating Alzheimer’s disease in the future.” The research team stressed that people should not be alarmed by their findings: Person-to-person transmission of Alzheimer's disease remains incredibly rare. “It is important to stress that the circumstances through which we believe these individuals tragically developed Alzheimer’s are highly unusual, and to reinforce that there is no risk that the disease can be spread between individuals or in routine medical care," said study co-author Jonathan Schott , a consultant neurologist at UCL Hospital. He is also chief medical officer at Alzheimer’s Research UK. "These findings do, however, provide potentially valuable insights into disease mechanisms," Collinge said. The findings "pave the way for further research which we hope will further our understanding of the causes of more typical, late onset Alzheimer’s disease.” There could be one practical consequence of the new study: An increased vigilance around the use and sterilization of medical instruments. “The recognition of transmission of amyloid-beta pathology in these rare situations should lead us to review measures to prevent accidental transmission via other medical or surgical procedures, in order to prevent such cases occurring in future," Collinge said. Writing in a Nature Medicine News & Views commentary, Dr. Mathias Jucker , of the University of Tubingen in Germany, and Lary Walker , of Emory University in Atlanta, said the study raises interesting points. First of all, they said, "it is imperative to stress that Alzheimer’s is not a contagious disease," and almost always emerges spontaneously within individual brains. However, they agreed with the British team that the, "report reinforces the potential of amyloid-beta seeds as targets for early prevention, and it underscores the importance of informed caution in the preparation of surgical instruments, handling of tissues and implementation of therapeutic biologics, particularly those derived from human sources." Sources University College London, news release, Jan. 29, 2024 Nature Medicine, Jan. 29, 2024 Disclaimer: Statistical data in medical articles provide general trends and do not pertain to individuals. Individual factors can vary greatly. Always seek personalized medical advice for individual healthcare decisions. Posted January 2024 More news resources FDA Medwatch Drug Alerts Daily MedNews News for Health Professionals New Drug Approvals New Drug Applications Drug Shortages Clinical Trial Results Generic Drug Approvals Subscribe to our newsletter Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

BERWYN, Pa., Sept. 13, 2022 /PRNewswire/ -- (NYSE: ANVS) Annovis Bio ("Annovis" or the "Company"), a clinical-stage drug platform company addressing neurodegenerative diseases, announced today the publication of three granted US patents – US11400075 (link), US11376238 (link), and US11382893 (link). The patents cover methods of treating amyloid lateral sclerosis (ALS), Huntington's disease, and prion diseases by administering buntanetap. They will provide intellectual property protection through 2031, prior to any patent extensions. The patents strengthen and expand the Company's intellectual property portfolio. The Company now has issued patents covering a wide range of neurodegenerative diseases, including Alzheimer's disease (AD), alpha-synucleopathies, such as Parkinson's disease (PD), tauopathies, such as frontotemporal dementia (FTD), chronic traumatic encephalopathy (CTE) and acute injuries such as stroke and traumatic brain injury. "These additional patents represent further proof for our platform drug, buntanetap, which acts on a variety of neurodegenerative disorders by inhibiting multiple neurotoxic proteins," said Maria L. Maccecchini, Ph.D., Founder, President, and CEO of Annovis. Summary of key coverage: A method of treating amyloid lateral sclerosis, a rare progressive neurodegenerative disorder, by administering buntanetap and inhibiting the synthesis of superoxide dismutase protein1 and TDP43. A method of treating Huntington's disease, a rare progressive neurodegenerative disorder, by administering buntanetap and inhibiting the synthesis of Huntingtin protein. A method of treating prion diseases, a family of ultra-rare progressive neurodegenerative disorders, by administering buntanetap. There is additional coverage of particular Prion diseases, including scrapie prion, transmissible mink encephalopathy (TME), chronic wasting disease (CWD), bovine spongiform encephalopathy (BSE) prion, feline spongiform encephalopathy (FSE), exotic ungulate encephalopathy (EUE), kuru prion, Creutzfeldt-Jakob disease (CJD), Variant Creutzfeldt-Jakob disease (vCJD, nvCJD), Gerst-mann-Straussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI) prion. About Buntanetap Buntanetap (previously known as ANVS401 or Posiphen) is an oral translational inhibitor of neurotoxic aggregating proteins (TINAPs), which mode of action leads to a lower level of neurotoxic proteins and consequently less toxicity in the brain. In a Phase 2a clinical trial in AD and PD patients, buntanetap was shown to be well-tolerated and safe, and its pharmacokinetics were found to be in line with levels measured earlier in humans, meeting both the primary and secondary endpoints. Additionally, exploratory endpoints were also met, as treatment with buntanetap resulted in statistically significant improvement in motor function in PD patients and cognition in AD patients. Presently buntanetap is being studied in a phase 3 early PD study and will enter a phase 2/3 study in AD patients later in the year. About Annovis Bio, Inc. Headquartered in Berwyn, Pennsylvania, Annovis Bio, Inc. is a clinical-stage, drug platform company developing transformative therapies that treat neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and other chronic and acute neurodegenerative diseases. The Company believes that it is the only company developing a drug that inhibits more than one neurotoxic protein, improves the information highway of the nerve cell, known as axonal transport, reduces inflammation and protects nerve cells from dying in chronic and acute neurodegeneration. Annovis conducted two Phase 2 studies: one in AD patients and one in both AD and PD patients. In the AD/PD study, buntanetap showed improvements in cognition and memory in AD as well as body and brain function in PD patients. For more information on Annovis Bio, please visit the Company's website and follow us on LinkedIn and Twitter. Forward-Looking Statements Statements in this press release contain "forward-looking statements" that are subject to substantial risks and uncertainties. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "expect," "believe," "will," "may," "should," "estimate," "project," "outlook," "forecast" or other similar words, and include, without limitation, statements regarding the timing, effectiveness, and anticipated results of buntanetap clinical trials. Forward-looking statements are based on Annovis Bio, Inc.'s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are described more fully in the section titled "Risk Factors" in the Annual Report on Form 10-K for the year ended December 31, 2021, filed with the Securities and Exchange Commission. Forward-looking statements contained in this announcement are made as of this date, and Annovis Bio, Inc. undertakes no duty to update such information except as required under applicable law. Media and Investor Contact: Nic Johnson Russo Partners, LLC (303) 482-6405 nic.johnson@russopartnersllc.com Company Codes: NYSE:ANVS

In a new study, researchers have identified the structure of protein fibrils linked to a hereditary form of human prion disease. This insight, they say, reveals the mechanism for how prions can jump between some animal species, while retaining a transmissibility barrier between other species. In a new study, researchers from the Case Western Reserve University School of Medicine have identified the structure of protein fibrils linked to a hereditary form of human prion disease. This insight, they say, reveals the mechanism for how prions can jump between some animal species, while retaining a transmissibility barrier between other species. While their findings have no immediate implications for the development of new therapies for more common human prion disorders such as Creutzfeldt-Jakob disease, the work does suggest the potential for disease to be transmitted from one species to another can be predicted based on structural information. "One of the major remaining questions in the field of prion diseases has been why these diseases are transmissible between some animal species but not others," said Witold Surewicz, a professor in the Department of Physiology and Biophysics at the School of Medicine and the study's senior author. "Our findings explain how this works." The study, funded by the National Institutes of Health, was published Sept. 12 in the scientific journal Nature Structural & Molecular Biology. Qiuye Li, a postdoctoral fellow at the School of Medicine, was lead author. The study was co-authored by Christopher Jaroniec, a professor of chemistry and biochemistry at Ohio State University. Prion diseases, also known as "transmissible spongiform encephalopathies," are a group of infectious brain-wasting disorders that include, among others, Creuzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (mad cow disease) in cattle and chronic wasting disease in deer and elk. These fatal disorders are unique because of their infectious pathogen -- which is not a virus but an abnormally shaped form of the prion protein. This misshaped protein assembles into long fibrils that spread by acting as a template -- or "seed" -- that binds to normal prion protein and forces it to change shape into an abnormal, disease-causing form, Surewicz said. While abnormally shaped proteins can readily act as templates to convert normal prion proteins from the same species, cross-seeding is believed to be restricted due to species-dependent differences in the sequence of amino acids -- the basic building blocks of each protein. "It appears that the barriers -- or lack thereof -- are fully dictated by the ability of prion protein from one species to adopt the structure of prion fibril seeds from another species," Li said. "This, in turn, depends on differences in amino acid at key structure-determining positions." Previously, scientists in the Surewicz laboratory developed a model employing a truncated form of prion proteins that allowed them to study in the test tube the mechanisms of prion propagation, including the phenomenon of transmissibility (seeding) barriers. However, full understanding of these mechanisms was hindered by the lack of information regarding the structure of infectious fibrils formed by these proteins. The authors overcame this fundamental limitation through use of a technique of cryo-electron microscopy -- a type of microscopy in which images are collected at very low temperature. By analyzing in the computer thousands of images of fibrils formed by human and mouse model prion proteins, they determined the architecture of these fibrils at a resolution close to individual atoms. This structural insight allowed the researchers to explain, in precise structural terms, why prion transmissibility barriers exist between some species while no such barriers are observed between other species. "Even though our present studies were performed using a model system," Surewicz said, "the ability to rationalize and predict prion transmissibility barriers based on structural data has important practical implications, especially given the current epidemic of chronic-wasting disease among elk and deer in parts of the United States and Canada, and growing concerns regarding potential transmission of this disease to humans."