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Élan
Elan Corporation plc was a major drugs firm based in Dublin, Ireland, which had major interests in the United States. It was listed on the New York Stock Exchange as ELN, the Irish Stock Exchange as ELN.I, and the London Stock Exchange as ELN.L. In 2013, the company merged with Perrigo to form Perrigo Company PLC. History The company was founded in Ireland by American businessman Don Panoz in 1969. In the late 1990s, its value on the Irish Stock Exchange reached over €20bn. However, in 2002, an accounting scandal and investor reactions to the global slump, caused a major devaluation resulting in a share price slump of over 90%. In July 2010, Élan was fined $203m for its marketing of epilepsy drugs. In February 2013, Elan decided to dispose of the rights to sell Tysabri to Biogen Idec for $3.25 billion. Products in development In neurology, Elan was focused on building upon its research and experience in the area of neuropathologies such as Alzheimer’s disease, whe ...
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Public Company
A public company is a company whose ownership is organized via shares of stock which are intended to be freely traded on a stock exchange or in over-the-counter markets. A public (publicly traded) company can be listed on a stock exchange (listed company), which facilitates the trade of shares, or not (unlisted public company). In some jurisdictions, public companies over a certain size must be listed on an exchange. In most cases, public companies are ''private'' enterprises in the ''private'' sector, and "public" emphasizes their reporting and trading on the public markets. Public companies are formed within the legal systems of particular states, and therefore have associations and formal designations which are distinct and separate in the polity in which they reside. In the United States, for example, a public company is usually a type of corporation (though a corporation need not be a public company), in the United Kingdom it is usually a public limited company (plc), i ...
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Biogen Idec
Biogen Inc. is an American multinational biotechnology company based in Cambridge, Massachusetts, specializing in the discovery, development, and delivery of therapies for the treatment of neurological diseases to patients worldwide. History Biogen was founded in 1978 in Geneva as ''Biotechnology Geneva'' by several prominent biologists, including Kenneth Murray from the University of Edinburgh, Phillip Allen Sharp from the Massachusetts Institute of Technology, Walter Gilbert from Harvard University (Gilbert served as CEO during the start-up phase of Biogen), Heinz Schaller from the University of Heidelberg, and Charles Weissmann from the University of Zurich (Weissmann contributed the first product interferon alpha).Werner Grundlehner''Zürcher Antikörper gegen Alzheimer hat Milliardenpotenzial – und Gegenwind.''Neue Zürcher Zeitung, June 8, 2021. Retrieved June 8, 2021. Gilbert and Sharp were subsequently honored with Nobel Prizes: Gilbert was recognized in 1980 with th ...
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Antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope (analogous to a lock) that is specific for one particular epitope (analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can ''tag'' a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly (for example, by blocking a part of a virus that is essential for its invasion). To allow the immune system to recognize millions of different antigens, the antigen-binding sites at both tips of the antibody come in an equally wide variety. In contrast, the remainder of the antibody is relatively constant. It only occurs in a few varia ...
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Bapineuzumab
Bapineuzumab (nicknamed "bapi") is a humanized monoclonal antibody that acts on the nervous system and may have potential therapeutic value for the treatment of Alzheimer's disease and possibly glaucoma. However, in 2012 it failed to produce significant cognitive improvements in patients in two major trials, despite lowering key biomarkers of AD, amyloid brain plaque and hyperphosphorylated tau protein in CSF. Bapineuzumab has been shown to recognise the extreme N-terminal 5 residues of Aβ peptide in a helical conformation (4HIX.pdb) stabilized by internal hydrogen bonds involving the first three amino acids. Bapineuzumab is an antibody to the beta-amyloid (Aβ) plaques that are believed to underlie Alzheimer's disease neuropathology. In previous clinical trials for vaccination against human beta amyloid, called AN-1792, patients with Alzheimer's disease using active immunization had positive outcomes with removal of plaques, but 6% of subjects developed aseptic meningitis and ...
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Phase III Clinical Trial
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for safety in a few human subjects, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays. Summary Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are 'post-marketing' or 'surveillance' studies conducted to monitor safety over sever ...
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Wyeth
Wyeth, LLC was an American pharmaceutical company. The company was founded in Philadelphia, Pennsylvania, in 1860 as ''John Wyeth and Brother''. It was later known, in the early 1930s, as American Home Products, before being renamed to Wyeth in 2002. Its headquarters moved to Collegeville, Pennsylvania and Madison, New Jersey, before they were consolidated with Pfizer's in New York City after the 2009 merger. Most of Wyeth's pharmaceutical assets were acquired by Pfizer in 2009, while its infant and maternal nutrition business was acquired by Nestlé in 2012. Wyeth manufactured over-the-counter drugs (OTCs) Robitussin and the analgesic Advil (ibuprofen) as well as prescription drugs Premarin and Effexor. History 1860–1899 In 1860, pharmacists John (1834–1907) and Frank Wyeth opened a drugstore with a small research lab on Walnut Street in Philadelphia. In 1862, on the suggestion of doctors, they began to manufacture large quantities of commonly ordered medicines ...
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Parkinson's Disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms become more common. The most obvious early symptoms are tremor, rigidity, slowness of movement, and difficulty with walking. Cognitive and behavioral problems may also occur with depression, anxiety, and apathy occurring in many people with PD. Parkinson's disease dementia becomes common in the advanced stages of the disease. Those with Parkinson's can also have problems with their sleep and sensory systems. The motor symptoms of the disease result from the death of cells in the substantia nigra, a region of the midbrain, leading to a dopamine deficit. The cause of this cell death is poorly understood, but involves the build-up of misfolded proteins into Lewy bodies in the neurons. Collectively, the main motor symptoms are also known as ...
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Neurodegeneration
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies (like proteinopathy) and induced cell death. These similarities suggest that ...
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Semagacestat
Semagacestat (LY-450139) was a candidate drug for a causal therapy against Alzheimer's disease. It was originally developed by Eli Lilly and Elan, and clinical trials were conducted by Eli Lilly. Phase III trials included over 3000 patients, but in August 2010, a disappointing interim analysis, in which semagacestat performed worse than the placebo, led to the trials being stopped. Mechanism of action β-Amyloid is a peptide of 39 to 43 amino acids. The isoforms with 40 and 42 amino acids (Aβ40/42) are the main constituents of amyloid plaques in the brains of Alzheimer's disease patients. β-Amyloid is formed by proteolysis of amyloid precursor protein (APP). Research on laboratory rats suggest that the soluble form of this peptide is a causative agent in the development of Alzheimer's. Semagacestat blocks the enzyme γ-secretase, which (along with β-secretase) is responsible for APP proteolysis. Clinical trials Phase III double-blind clinical trials started in March 200 ...
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Amyloid Plaques
Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of microglia and astrocytes can be associated with amyloid plaques. Some plaques occur in the brain as a result of aging, but large numbers of plaques and neurofibrillary tangles are characteristic features of Alzheimer's disease. Abnormal neurites in amyloid plaques are tortuous, often swollen axons and dendrites. The neurites contain a variety of organelles and cellular debris, and many of them include characteristic paired helical filaments, the ultrastructural component of neurofibrillary tangles. The plaques are highly variable in shape and size; in tissue sections immunostained for Aβ, they comprise a log-normal size distribution curve with an average plaque area of 400-450 square micrometers (µm²). The smallest plaques (less than 200 ...
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Gamma Secretase
Gamma secretase is a multi-subunit protease complex, itself an integral membrane protein, that cleaves single-pass transmembrane proteins at residues within the transmembrane domain. Proteases of this type are known as intramembrane proteases. The most well-known substrate of gamma secretase is amyloid precursor protein, a large integral membrane protein that, when cleaved by both gamma and beta secretase, produces a short 37-43 amino acid peptide called amyloid beta whose abnormally folded fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients. Gamma secretase is also critical in the related processing of several other type I integral membrane proteins, such as Notch, ErbB4, E-cadherin, N-cadherin, ephrin-B2, or CD44. Subunits and assembly The gamma secretase complex consists of four individual proteins: PSEN1 (presenilin-1), nicastrin, APH-1 (anterior pharynx-defective 1), and PEN-2 (presenilin enhancer 2). Recent evidenc ...
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Beta Secretase
Beta-secretase 1, also known as beta-site amyloid precursor protein cleaving enzyme 1, beta-site APP cleaving enzyme 1 (BACE1), membrane-associated aspartic protease 2, memapsin-2, aspartyl protease 2, and ASP2, is an enzyme that in humans is encoded by the ''BACE1'' gene. Expression of BACE1 is observed mainly in neurons. BACE1 is an aspartic acid protease important in the formation of myelin sheaths in peripheral nerve cells: in mice the expression of BACE1 is high in the postnatal stages, when myelination occurs. * The transmembrane protein contains two active site aspartate residues in its extracellular protein domain and may function as a dimer, its cytoplasmic tail is required for the correct maturation and an efficient intracellular trafficking, but doesn't affect the activity. It is produced as a pro-enzyme, the endoproteolitc removal occurs after BACE leaves Endoplasmic reticulum, in the Golgi apparatus. In addition the pro-peptide receives additional sugars to increase t ...
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