Michael Hollingshead (?–1984?) was a British researcher who studied psychedelic drugs , including psilocybin and LSD , at Harvard University in the mid-20th century. He was the father of comedian Vanessa Hollingshead . He evangelized the use of LSD to many notable figures.
85-620: Hollingshead was the Executive Secretary for the Institute of British-American Cultural Exchange in 1961. Dr. John Beresford, a research scientist, received a package of one gram of LSD from Sandoz Laboratories in Switzerland at a time when it was still legal to experiment with it. Beresford, in turn, gave part of the gram to Hollingshead. One of Hollingshead's experiments studied the effects on web-weaving by spiders under
170-459: A condensation domain , and an N-methyltransferase domain. The adenylation domain is responsible for substrate recognition and activation, whereas the thiolation domain covalently binds the adenylated amino acids to phosphopantetheine , and the condensation domain elongates the peptide chain. Cyclosporin synthetase substrates include L- valine , L- leucine , L- alanine , glycine , 2-aminobutyric acid , 4-methyl threonine , and D-alanine , which
255-558: A dyewood mill and a dye extraction plant. Two years later, they began the production of synthetic fuchsine. In 1901, they formed the public limited company Geigy, and the name of the company was changed to J. R. Geigy Ltd in 1914. CIBA and Geigy merged in 1970 to form Ciba‑Geigy Ltd. / ˌ s iː b ə ˈ ɡ aɪ ɡ i / . In the mid-1990s, state and federal health and environmental agencies identified an increased incidence of childhood cancers in Toms River, New Jersey , from
340-580: A generic medication . Ciclosporin is indicated to treat and prevent graft-versus-host disease in bone marrow transplantation and to prevent rejection of kidney , heart , and liver transplants . It is also approved in the US for treating of rheumatoid arthritis and psoriasis , persistent nummular keratitis following adenoviral keratoconjunctivitis , and as eye drops for treating dry eyes caused by Sjögren's syndrome and meibomian gland dysfunction. In addition to these indications, ciclosporin
425-517: A 15 percent stake in Gamida Cell for $ 35 million, with the option to purchase the whole company for approximately $ 165 million. In October 2014, Novartis announced its intention to sell its influenza vaccine business (inclusive of its development pipeline), subject to regulatory approval, to CSL for $ 275 million. In March 2015, the company announced BioPharma had completed its acquisition of two Phase III cancer-drug candidates;
510-432: A 47 percent premium. In March 2018, GlaxoSmithKline announced that it has reached an agreement with Novartis to acquire Novartis' 36.5 percent stake in their Consumer Healthcare Joint Venture for $ 13 billion (£9.2 billion). In April of the same year, the business utilised some of the proceeds from the aforementioned GlaxoSmithKline deal to acquire Avexis for $ 218 per share or $ 8.7 billion in total, gaining
595-422: A better subjective understanding of the schizophrenic experience, and many did exactly that and so did other scientific researchers. The Sandoz product received mass publicity as early as 1954, in a Time magazine feature. Research on LSD peaked in the 1950s and early 1960s. The CIA purchased quantities of LSD from Sandoz for use in its illegal human experimentation program known as MKUltra . Sandoz withdrew
680-522: A clinical-stage SK channel positive allosteric modulator. In September 2021, the company announced it would acquire gene-therapy business, Arctos Medical, broadening its optogenetics range. In December, Novartis announced it would purchase Gyroscope Therapeutics from health care investment company, Syncona Ltd, for up to $ 1.5 billion. In February 2022, New York City-based biotechnology company Cambrian Biopharma announced it had licensed rights to mTOR inhibitor programs from Novartis. As part of
765-481: A developer of technology for delivering RNA-based therapies, upfront for $ 500 million and an additional $ 500 million subject to reaching certain targets. Also in June, Novartis announced it would it would sell Xiidra to Bausch & Lomb for $ 1.75 billion and receive additional $ 750 million linked to future sales for Xiidra as well as two pipeline assets. In September 2023, Novartis announced that
850-573: A fire broke out in a production plant storage room, which led to the Sandoz chemical spill and a large amount of pesticide being released into the upper Rhine river. This exposure killed many fish and other aquatic life. In 1995, Sandoz spun off its specialty chemicals business to form Clariant . In 1997, Clariant merged with the specialty chemicals business that was spun off from Hoechst AG in Germany. In 1996, Ciba-Geigy merged with Sandoz, with
935-533: A new company, Syngenta . In 2003, Novartis organized all its generics businesses into one division, and merged some of its subsidiaries into one company, reusing the predecessor brand name of Sandoz. In 2005, Novartis expanded its subsidiary Sandoz significantly through the US$ 8.29 billion acquisition of Hexal, one of Germany's leading generic drug companies, and Eon Labs, a fast-growing United States generic pharmaceutical company. In 2006, Novartis acquired
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#17327810619471020-472: A newly created subsidiary. Endocyte will bolster Novartis' offering in its radiopharmaceuticals business, with Endocyte's first in class candidate Lu-PSMA-617 being targeted against metastatic castration-resistant prostate cancer. In late December the company announced it would acquire France-based contract manufacturer, CellforCure from LFB , boosting its capacity to produce cell and gene therapies. On 9 April 2019, Novartis announced that it had completed
1105-524: A remission of proteinuria caused by such diseases as MCD and FSGS. Ciclosporin blocks the calcineurin-mediated dephosphorylation of synaptopodin, a regulator of Rho GTPases in podocytes, thereby preserving the phosphorylation-dependent synaptopodin-14-3-3 beta interaction. Preservation of this interaction, in turn, protects synaptopodin from cathepsin L-mediated degradation. Altogether, the antiproteinuric effect of Ciclosporin results, at least in part, from
1190-655: A strong foundation for our (Novartis') individualized treatment programs". In 2012, the Company cut approximately 2,000 positions in the United States, primarily in sales, in response to anticipated revenue downturns from the hypertension drug Diovan , which was losing patent protection, and the realization that the anticipated successor to Diovan, Rasilez , was failing in clinical trials. The 2012 personnel reductions follow ~2000 cut positions in Switzerland and
1275-646: A topical emulsion of ciclosporin for treating inflammation caused by keratoconjunctivitis sicca (dry eye syndrome) has been marketed under the brand name Restasis. Ikervis is a similar formulation with a concentration of 0.1%. Inhaled ciclosporin formulations are in clinical development, and include a solution in propylene glycol and liposome dispersions. Ciclosporin is in a phase II/III (adaptive) clinical study in Europe to determine its ability to ameliorate neuronal cellular damage and reperfusion injury (phase III) in traumatic brain injury. This multi-center study
1360-654: Is Novaliq GmbH. Vevizye was authorized for medical use in the European Union in September 2024. The natural product was named cyclosporin by the German-speaking scientists who first isolated it and cyclosporine when translated into English. Per International Nonproprietary Name (INN) guidelines for drugs, the y was replaced with i so that the INN for the medication is spelled ciclosporin. Ciclosporin
1445-589: Is a calcineurin inhibitor , used as an immunosuppressant medication . It is taken orally or intravenously for rheumatoid arthritis , psoriasis , Crohn's disease , nephrotic syndrome , eczema , and in organ transplants to prevent rejection . It is also used as eye drops for keratoconjunctivitis sicca (dry eyes). Common side effects include high blood pressure, headache, kidney problems , increased hair growth, and vomiting. Other severe side effects include an increased risk of infection, liver problems, and an increased risk of lymphoma . Blood levels of
1530-746: Is a full member of the European Federation of Pharmaceutical Industries and Associations (EFPIA), the Biotechnology Innovation Organization (BIO), the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), and the Pharmaceutical Research and Manufacturers of America (PhRMA). Novartis is the third most valuable pharmaceutical company in Europe, after Novo Nordisk and Roche . Novartis
1615-442: Is already working on in 'real-life' situations". The deal will pursue solutions for "organizing and using" data generated from Novartis' laboratory experiments, clinical trials, and manufacturing plants. It will also look at improving manufacturing of Chimeric antigen receptor T cell (CAR T cells). Finally, the deal "will also apply AI to generative chemistry to enhance drug design". In November 2019, Sandoz announced it would acquire
1700-597: Is also eligible to receive up to $ 300 million dependent upon future marketing approval milestones outside of America and up to $ 400 million relating to sales milestones. In September 2014, Ophthotech received its first $ 50 million phase III trial milestone payment from Novartis. In April 2014, Novartis announced that it would acquire GlaxoSmithKline 's cancer drug business for $ 16 billion as well as selling its vaccines business to GlaxoSmithKline for $ 7.1 billion. In August 2014 Genetic Engineering & Biotechnology News reported that Novartis had acquired
1785-527: Is also used in severe atopic dermatitis , It has been used in severe rheumatoid arthritis and related diseases. Ciclosporin has also been used in people with acute severe ulcerative colitis and hives that do not respond to treatment with steroids . Side effects of ciclosporin can include gum enlargement , increased hair growth, convulsions , peptic ulcers , pancreatitis , fever , vomiting , diarrhea , confusion , increased cholesterol , trouble breathing , numbness and tingling (particularly of
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#17327810619471870-503: Is being organized by NeuroVive Pharma and the European Brain Injury Consortium using NeuroVive's formulation of ciclosporin called Neurostat (also known by its cardioprotection brand name of Ciclomulsion). This formulation uses a lipid emulsion base instead of cremophor and ethanol. NeuroSTAT was compared to Sandimmune in a phase I study and found to be bioequivalent. In this study, NeuroSTAT did not exhibit
1955-400: Is highly metabolized in humans and animals after ingestion. The metabolites, which include cyclosporin B, C, D, E, H, and L, have less than 10% of ciclosporin's immunosuppressant activity and are associated with higher kidney toxicity. Cyclosporin is synthesized by a nonribosomal peptide synthetase, cyclosporin synthetase. The enzyme contains an adenylation domain, a thiolation domain,
2040-563: Is the INN and the British Approved Name (BAN), while cyclosporine is the United States Adopted Name (USAN) and cyclosporin is a former BAN. Ciclosporin exhibits very poor solubility in water, and, as a consequence, suspension and emulsion forms of the medication have been developed for oral administration and for injection. Ciclosporin was originally brought to market by Sandoz (now Novartis ), under
2125-502: Is the cyclosporin synthetase, SimB ( CAA02484.1 ) is the alanine racemase, and SimG (similar to ATQ39432.1 ) is the polyketide synthase. These genes are associated with an active retrotransposon. Although these sequences are poorly-annotated on GenBank and other databases, 90% similar sequences can be found for the Cyclosporin-producing Beauveria felina (or Amphichorda ~ ). SimB has two paralogs in
2210-490: Is the founder of Sandoz's pharmaceutical department in 1917. In 1918, Arthur Stoll isolated ergotamine from ergot ; the substance was eventually used to treat migraine and headaches and was introduced under the trade name Gynergen in 1921. Between the World Wars, Gynergen (1921) and Calcium-Sandoz (1929) were brought to market. Sandoz also produced chemicals for textiles, paper, and leather , beginning in 1929. In 1939,
2295-495: Is the starting amino acid in the biosynthetic process. With the adenylation domain, cyclosporin synthetase generates the acyl-adenylated amino acids, then covalently binds the amino acid to phosphopantetheine through a thioester linkage. Some of the amino acid substrates become N-methylated by S-adenosyl methionine . The cyclization step releases cyclosporin from the enzyme . Amino acids such as D-Ala and butenyl-methyl-L-threonine (Bmt) indicate cyclosporin synthetase requires
2380-475: Is thus recommended that the lowest effective dose for people requiring long-term treatment be used. Ciclosporin use after a kidney transplantation is associated with increased levels of uric acid in the blood and, in some cases, gout . Ciclosporin is listed as an IARC Group 1 carcinogen (i.e. there is sufficient evidence of carcinogenicity in humans), specifically leading to squamous cell skin cancer and non-Hodgkin lymphoma . Ciclosporin's main effect
2465-413: Is to lower the activity of T-cells ; it does so by inhibiting calcineurin in the calcineurin–phosphatase pathway and preventing the mitochondrial permeability transition pore from opening. Ciclosporin binds to the cytosolic protein cyclophilin (immunophilin) of lymphocytes , especially of T cells. This cyclosporin—cyclophilin complex inhibits calcineurin , which is normally responsible for activating
2550-558: The CD20 monoclonal antibody Ofatumumab from GlaxoSmithKline for up to $ 1 billion. In October the company acquired Admune Therapeutics for an undisclosed sum, as well as licensing PBF-509 , an adenosine A2A receptor antagonist which is in Phase I clinical trials for non-small cell lung cancer, from Palobiofarma . In November 2016, the company announced it would acquire Selexys Pharmaceuticals for $ 665 million. In December,
2635-809: The Gerber Products Company to Nestlé as part of its continuing effort to shed old Sandoz and Ciba-Geigy businesses and focus on healthcare. In 2009, Novartis reached an agreement to acquire an 85 percent stake in the Chinese vaccines company Zhejiang Tianyuan Bio-Pharmaceutical Co., Ltd. as part of a strategic initiative to build a vaccines industry leader in this country and expand the group's limited presence in this fast-growing market segment. This proposed acquisition will require government and regulatory approvals in China. In 2010, Novartis offered to pay US$ 39.3 billion to fully acquire Alcon ,
Michael Hollingshead - Misplaced Pages Continue
2720-504: The MEK inhibitor binimetinib (MEK 162) and the BRAF inhibitor encorafenib (LGX818), for $ 85 million. In addition, the company sold its RNAi portfolio to Arrowhead Research for $ 10 million and $ 25 million in stock. In June, the company announced it would acquire Spinifex Pharmaceuticals for more than $ 200 million. In August, the company acquired the remaining rights to
2805-541: The 1970–1995 period. Multiple investigations by state and federal environmental and health agencies indicated that the likely source of the increased cancer risk was contamination from Toms River Chemical Plant (then operated by Ciba-Geigy), which had been in operation since 1952, and the Reich Farm/Union Carbide. The area was designated a United States Environmental Protection Agency Superfund site in 1983 after an underground plume of toxic chemicals
2890-811: The Beatles . Sandoz Laboratories Novartis AG is a Swiss multinational pharmaceutical corporation based in Basel , Switzerland. Consistently ranked in the global top five, Novartis is one of the largest pharmaceutical companies in the world and was the fourth largest by revenue in 2022. Novartis manufactures the drugs clozapine (Clozaril), diclofenac (Voltaren; sold to GlaxoSmithKline in 2015 deal), carbamazepine (Tegretol), valsartan (Diovan), imatinib mesylate (Gleevec/Glivec), cyclosporine (Neoral/Sandimmune), letrozole (Femara), methylphenidate (Ritalin; production ceased 2020), terbinafine (Lamisil), deferasirox (Exjade), and others. Novartis
2975-597: The California-based Chiron Corporation . Chiron had been divided into three units: Chiron Vaccines, Chiron Blood Testing, and Chiron BioPharmaceuticals. The biopharmaceutical unit was integrated into Novartis Pharmaceuticals, while the vaccines and blood testing units were made into a new Novartis Vaccines and Diagnostics division. Also in 2006, Sandoz became the first company to have a biosimilar drug approved in Europe with its recombinant human growth hormone drug. In 2007, Novartis sold
3060-617: The German chemical maker BASF . In 1998, the company entered into a biotechnology licensing agreement with the University of California at Berkeley Department of Plant and Microbial Biology . Critics of the agreement expressed concern over prospects that the agreement would diminish academic objectivity, or lead to the commercialization of genetically modified plants. The agreement expired in 2003. In 2000, Novartis and AstraZeneca combined their agrobusiness divisions to create
3145-554: The Japanese business of Aspen Global inc for €300 million (around $ 330 million), boosting the business's presence in Asia. In late November 2019, the business announced it would acquire The Medicines Company for US$ 9.7 billion ($ 85 per share) in order to acquire amongst other assets, the cholesterol lowering therapy; inclisiran . In April 2020, the company announced it would acquire Amblyotech. In September 2020, Novartis
3230-748: The Novartis drugs. In October Novartis announced it would acquire Vedere Bio for $ 280 million boosting the businesses cell and gene therapy offerings. In October 2020, as part of a joint venture to develop therapeutic drugs to combat COVID-19 , Novartis bought 6% of all shares outstanding in Swiss DARPin research company Molecular Partners AG at CHF 23 per share. In December 2020, Novartis announced it would acquire Cadent Therapeutics for up to $ 770 million, gaining full rights to CAD-9303 (a NMDAr positive allosteric modulator ), MIJ-821 (a NMDAr negative allosteric modulator ) and CAD-1883
3315-568: The Toms River water system has been subject to the most stringent water testing in New Jersey and is considered safe for consumption. Dan Fagin 's Toms River: A Story of Science and Salvation , the 2014 Pulitzer Prize winning book, examined the issue of industrial pollution at the site in detail. Sandoz is the generic drugs division of Novartis. Before the 1996 merger with Ciba-Geigy to form Novartis, Sandoz Pharmaceuticals (Sandoz AG)
3400-552: The United States in 2011, ~1400 cut positions in the United States in 2010, and a reduction of "thousands" and several site closures in previous years. Also in 2012, Novartis became the biggest manufacturer of generic skin care medicine, after agreeing to buy Fougera Pharmaceuticals for $ 1.525 billion in cash. In 2013, the Indian Supreme Court issued a decision rejecting Novartis' patent application in India on
3485-451: The action of other enzymes. The racemization of L-Ala to D-Ala by alanine racemase is pyridoxal phosphate -dependent. The formation of butenyl-methyl-L-threonine is performed by a Bmt polyketide synthase that uses acetate/malonate as its starting material. Tolypocladium inflatum , the species currently used for mass production of Cyclosporin, has the biosynthetic genes arranged into a 12-gene cluster. Of these 12 genes, SimA ( Q09164 )
Michael Hollingshead - Misplaced Pages Continue
3570-435: The anaphylactic and hypersensitivity reactions found in cremophor- and ethanol-based products. Ciclosporin has been investigated as a possible neuroprotective agent in conditions such as traumatic brain injury , and has been shown in animal experiments to reduce brain damage associated with injury. Ciclosporin blocks the formation of the mitochondrial permeability transition pore , which has been found to cause much of
3655-576: The brand name Sandimmune, which is available as soft gelatin capsules, an oral solution, and a formulation for intravenous administration. These are all nonaqueous compositions. A newer microemulsion , orally-administered formulation, Neoral, is available as a solution and as soft gelatin capsules. Compositions of Neoral are designed to form microemulsions in contact with water. Generic ciclosporin preparations have been marketed under various brand names, including Cicloral (by Sandoz/Hexal), Gengraf (by Abbott ) and Deximune (by Dexcel Pharma ). Since 2002,
3740-482: The company Bindschedler and Busch. In 1884, Bindschedler and Busch was transformed into a joint-stock company named " Gesellschaft für Chemische Industrie Basel " (Company for Chemical Industry Basel). The acronym , CIBA, was adopted as the company's name in 1945. The foundation for Geigy was established in 1857, when Johann Rudolf Geigy-Merian (1830–1917) and Johann Muller-Pack acquired a site in Basel, where they built
3825-453: The company acquired Encore Vision , gaining the company's principle compound, EV06, is a first-in-class topical therapy for presbyopia . In December Novartis acquired Ziarco Group Limited, bolstering its presence in eczema treatments. In late October 2017, Reuters announced that Novartis would acquire Advanced Accelerator Applications for $ 3.9 billion, paying $ 41 per ordinary share and $ 82 per American depositary share representing
3910-610: The company began producing agricultural chemicals. The psychedelic effects of lysergic acid diethylamide (LSD) were discovered at the Sandoz laboratories in 1943 by Arthur Stoll and Albert Hofmann . Sandoz began clinical trials and marketed the substance, from 1947 through the mid-1960s, under the name Delysid as a psychiatric drug, thought useful for treating a wide variety of mental ailments , ranging from alcoholism to sexual deviancy . Sandoz suggested in its marketing literature that psychiatrists take LSD themselves, to gain
3995-539: The company violated the False Claims Act and Anti-Kickback Statute by paying physicians to induce them to prescribe certain of the company's drugs. Novartis allegedly spent hundreds of millions of dollars on fraudulent speaker programs that served as a means to bribe doctors with cash payments and other extravagant rewards. Many of these speaking programs were allegedly nothing more than social gatherings at expensive restaurants, with limited or no discussion about
4080-870: The core material for Masters' and Houston's work The Varieties of Psychedelic Experience . In 1965, he moved to London and opened the World Psychedelic Center. He also worked in experimental film, collaborating on the Scott Bartlett short subject "A Trip to the Moon", in 1968. Hollingshead was an associate of the Castalia Foundation , a contributor to the Psychedelic Review , and interviewed cult writer Robert Anton Wilson for High Times magazine in 1980. According to Psychedelia Britannica , Hollingswood died in
4165-435: The damage associated with head injury and neurodegenerative diseases . Ciclosporin's neuroprotective properties were first discovered in the early 1990s when two researchers (Eskil Elmér and Hiroyuki Uchino) were conducting experiments in cell transplantation. An unintended finding was that cyclosporin A was strongly neuroprotective when it crossed the blood–brain barrier. This same process of mitochondrial destruction through
4250-542: The deal, Cambrian was setting up a subsidiary called Tornado Therapeutics. In August 2022, the company announced its plan to spin off Sandoz generic drugs unit to form a publicly traded business as part of a restructuring. With the unit having generated US$ 9.69 billion in 2021, the spin-off would create the biggest generic drugs company in Europe by sales. In June 2023, Novartis announced it would acquire Chinook Therapeutics and its drug pipeline for up to $ 3.5 billion. In July 2023, Novartis acquired DTx Pharma,
4335-406: The dephosphorylation of NF-AT, leads to reduced effector T-cell function ; it does not affect cytostatic activity. Ciclosporin also binds to the cyclophilin D protein that constitutes part of the mitochondrial permeability transition pore (MPTP), thus preventing MPTP opening. The MPTP is found in the mitochondrial membrane of cardiac muscle cells. MPTP opening signifies a sudden change in
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#17327810619474420-537: The drug from the market in 1965. The drug became a cultural novelty of the 1960s after psychologist Timothy Leary at Harvard University began to promote its use for recreational and spiritual experiences among the general public. Sandoz opened its first foreign offices in 1964. In 1967, Sandoz merged with Wander AG (known for Ovomaltine and Isostar ). Sandoz acquired the companies Delmark , Wasabröd (a Swedish manufacturer of crisp bread ), and Gerber Products Company (a baby food company). On 1 November 1986,
4505-693: The early 1980s. In a 2018 interview, Hollingshead's daughter Vanessa said that her father died in Bolivia from a stomach ulcer in 1984. Apart from Leary, those Hollingshead is reputed to have introduced to LSD include writers William S. Burroughs and Paul Krassner , comparative religions scholar Huston Smith , philosopher Alan Watts , graphic designer Storm Thorgerson , film director Roman Polanski , poet Allen Ginsberg , businessman-financier Saul Steinberg , musicians Donovan , Keith Richards , Pete LaRoca , Charles Mingus , Maynard Ferguson and Paul McCartney , John Lennon , and George Harrison of
4590-404: The eyes of a transplant surgeon that ciclosporin was an epoch-making drug for solid organ allotransplantation. It greatly expanded the clinical applicability of such transplantation by substantially advancing the antirejection pharmacotherapy component. Put simply, the biggest limits of applying such transplantation more widely were not cost or surgical skill (as formidable as those are) but rather
4675-470: The final form of Gleevec , Novartis's cancer drug; the case caused great controversy. In 2013, Novartis was sued again by the US government, this time for allegedly bribing doctors for a decade so that their patients are steered towards the company's drugs. In January 2014, Novartis announced plans to cut 500 jobs from its pharmaceuticals division. In February 2014, Novartis announced that it acquired CoStim Pharmaceuticals. In May 2014, Novartis purchased
4760-534: The influence of the drug. Hollingshead claims to have first tried LSD by licking the spoon of a batch of LSD-laced cake icing he had packed in a mayonnaise jar for transport. (This jar was to become the object of psychedelic legend.) Following this first experience, Hollingshead contacted Aldous Huxley , who suggested he get in contact with Timothy Leary to discuss the potential of the drug. In September 1961, Hollingshead met Leary in Cambridge, Massachusetts , and
4845-420: The inner mitochondrial membrane permeability, allowing protons and other ions and solutes of a size up to ~1.5 kDa to go through the inner membrane. This change of permeability is considered a cellular catastrophe, leading to cell death. However, brief mitochondrial permeability transition pore openings play an essential physiological role in maintaining healthy mitochondrial homeostasis. Ciclosporin can induce
4930-455: The intracellular Ca to increase the contractility cycling rates. Constitutively high levels of mitochondrial Ca cause inappropriate MPTP opening leading to a decrease in the cardiac range of function, leading to cardiac hypertrophy as an attempt to compensate for the problem. Cyclosporin A has been shown to decrease cardiac hypertrophy by affecting cardiac myocytes in many ways. Cyclosporin A binds to cyclophilin D to block
5015-494: The lead compound AVXS-101 used to treat spinal muscular atrophy . In August 2018, Novartis signed a deal with Laekna-a Shanghai-based pharmaceutical company for its two clinical-stage cancer drugs. Novartis gave Laekna the exclusive international rights for the drugs that are oral pan-Akt kinase inhibitors namely; afuresertib (ASB138) and uprosertib (UPB795). In mid-October, the company announced it would acquire Endocyte Inc for $ 2.1 billion ($ 24 per share) merging it with
5100-434: The lips), itchiness , high blood pressure , potassium retention (possibly leading to hyperkalemia ), kidney and liver dysfunction, burning sensations at finger tips, and an increased vulnerability to opportunistic fungal and viral infections . Ciclosporin causes hypertension by inducing vasoconstriction in the kidneys and increasing sodium reabsorption. The increase in blood pressure can cause cardiovascular events; it
5185-416: The maintenance of synaptopodin protein abundance in podocytes, which, in turn, is sufficient to maintain the integrity of the glomerular filtration barrier and to safeguard against proteinuria. Ciclosporin is a cyclic peptide of 11 amino acids ; it contains a single D -amino acid , which is rarely encountered in nature. Unlike most peptides, ciclosporin is not synthesized by ribosomes. Ciclosporin
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#17327810619475270-400: The medication should be checked to decrease the risk of side effects. Use during pregnancy may result in preterm birth ; however, ciclosporin does not appear to cause birth defects . Ciclosporin is believed to work by decreasing the function of lymphocytes . It does this by forming a complex with cyclophilin to block the phosphatase activity of calcineurin , which in turn decreases
5355-447: The medication, the lower doses used in dogs mean the drug acts as an immunomodulator and has fewer side effects than in humans. The benefits of using this product include the reduced need for concurrent therapies to bring the condition under control. It is available as an ophthalmic ointment for dogs called Optimmune , manufactured by Intervet , which is part of Merck . It is also used to treat sebaceous adenitis (immune response against
5440-454: The opening of MPTP, and thus decreases the release of protein cytochrome C, which can cause programmed cell death. CypD is a protein within the MPTP that acts as a gate; binding by cyclosporin A decreases the amount of inappropriate opening of MPTP, which decreases the intramitochondrial Ca . Decreasing intramitochondrial Ca allows for reversal of cardiac hypertrophy caused in
5525-644: The opening of the MPT pore is implicated in making traumatic brain injuries much worse. Ciclosporin has been used experimentally to treat cardiac hypertrophy (an increase in cell volume). Inappropriate opening of the mitochondrial permeability transition pore (MPTP) manifests in ischemia (blood flow restriction to tissue) and reperfusion injury (damage occurring after ischemia when blood flow returns to tissue), after myocardial infarction (heart attack) and when mutations in mitochondrial DNA polymerase occur. The heart attempts to compensate for disease state by increasing
5610-406: The original cardiac response. Decreasing the release of cytochrome C caused decreased cell death during injury and disease. Cyclosporin A also inhibits the phosphatase calcineurin pathway (14). Inhibition of this pathway has been shown to decrease myocardial hypertrophy. The medication is approved in the United States for the treatment of atopic dermatitis in dogs. Unlike the human form of
5695-451: The pharmaceutical and agrochemical divisions of both staying together to form Novartis. Other Ciba-Geigy and Sandoz businesses were spun off as independent companies. notably Ciba Specialty Chemicals . Sandoz's Master Builders Technologies, a producer of chemicals for the construction industry, was sold off to SKW Trostberg A.G., a subsidiary of the German energy company VIAG , while its North American corn herbicide business became part of
5780-603: The problem of allograft rejection and the scarcity of donor organs. Ciclopsporin was a major advancement against the rejection part of the challenge. In July 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Vevizye, intended for the treatment of dry eye disease. The applicant for this medicinal product
5865-483: The production of inflammatory cytokines by T-lymphocytes . Ciclosporin was isolated in 1971 from the fungus Tolypocladium inflatum and came into medical use in 1983. It is on the World Health Organization's List of Essential Medicines . In 2022, it was the 185th most commonly prescribed medication in the United States, with more than 2 million prescriptions. It is available as
5950-462: The rights to market Ophthotech 's Fovista (an anti- PDGF aptamer , also being investigated for use in combination with anti- VEGF treatments) outside the U.S. for up to $ 1 billion. Novartis acquired exclusive rights to market the eye drug outside of the states while retaining U.S. marketing rights. The company agreed to pay Ophthotech $ 200 million upfront, and $ 130 million in milestone payments relating to Phase III trials. Ophthotech
6035-497: The same organism with different but overlapping functions thanks to their low specificity. In 1970, new strains of fungi were isolated from soil samples taken from Norway and from Wisconsin in the US by employees of Sandoz (now Novartis ) in Basel , Switzerland . Both strains produced a family of natural products called cyclosporins. Two related components that had antifungal activity were isolated from extracts from these fungi. The Norwegian strain, Tolypocladium inflatum Gams ,
6120-1018: The spin-off had been approved by its shareholders and that it would be completed by the next month, resulting in Novartis shareholders receiving one Sandoz share for every five Novartis shares. Sandoz will be listed on the SIX Swiss Exchange with a market capitalization between $ 18 billion and $ 25bn. On 4 October 2023, Novartis completed the spin-off of Sandoz as a stand-alone company. In November 2023, Legend Biotech and Novartis signed an out-license deal to develop and manufacture Legend's chimeric antigen receptor (CAR-T) therapies, that go after delta-like ligand protein 3 (DLL3) including large cell neuroendocrine carcinoma candidate LB2102 for $ 100 million upfront, and Legend Biotech will be eligible to receive up to $ 1.01 billion in clinical, regulatory, and commercial milestone payments and tiered royalties. Cyclosporine Ciclosporin , also spelled cyclosporine and cyclosporin ,
6205-463: The spin-off of Alcon as a separate commercial entity. Alcon was listed on the SIX exchange in Switzerland and NYSE exchange in the U.S. Novartis announced during late 2019 a five-year artificial intelligence "alliance" with Microsoft. The companies aim to create applications for "Microsoft's AI capabilities", in turn improving the other's drug development processes. Microsoft seeks to "test AI products it
6290-472: The transcription of interleukin 2 . In T-cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to activate calcineurin. Calcineurin then dephosphorylates the transcription factor NF-AT (nuclear factor of activated T-cells), which moves to the T-cell nucleus and increases the transcription of genes for IL-2 and related cytokines. Ciclosporin, by preventing
6375-463: The world's largest eye-care company, including a majority stake held by Nestlé. Novartis had bought 25 percent of Alcon in 2008. Novartis created a new division and called it Alcon, under which it placed its CIBA VISION subsidiary and Novartis Ophthalmics, which became the second-largest division of Novartis. The total cost for Alcon amounted to $ 60 billion. In 2011, Novartis acquired the medical laboratory diagnostics company Genoptix to "serve as
6460-448: Was a pharmaceutical company headquartered in Basel , Switzerland (as was Ciba-Geigy), and was best known for developing drugs such as Sandimmune for organ transplantation , the antipsychotic Clozaril , Mellaril Tablets and Serentil Tablets for treating psychiatric disorders , and Cafergot Tablets and Torecan Suppositories for treating migraine headaches . The Chemiefirma Kern und Sandoz ("Kern and Sandoz Chemistry Firm")
6545-417: Was created in 20 December 1996 from the merger of Ciba-Geigy and Sandoz Laboratories, both Swiss companies. Ciba-Geigy was formed in 1970 by the merger of J. R. Geigy Ltd (founded in Basel in 1857) and CIBA (founded in Basel in 1859). Ciba began in 1859, when Alexander Clavel (1805–1873) took up the production of fuchsine in his factory for silk -dyeing works in Basel. By 1873, he sold his dye factory to
6630-569: Was formed in 1996 by the merger of Ciba-Geigy and Sandoz . It was considered the largest corporate merger in history during that time. The pharmaceutical and agrochemical divisions of both companies formed Novartis as an independent entity. The name Novartis was based on the Latin terms, “novae artes” (new skills). After the merger, other Ciba-Geigy and Sandoz businesses were sold, or, like Ciba Specialty Chemicals , spun off as independent companies. The Sandoz brand disappeared for three years, but
6715-489: Was founded in 1886 by Alfred Kern (1850–1893) and Edouard Sandoz (1853–1928). The first dyes manufactured by them were alizarinblue and auramine . After Kern's death, the partnership became the corporation Chemische Fabrik vormals Sandoz in 1895. The company began producing the fever-reducing drug antipyrin in the same year. In 1899, the company began producing the sugar substitute saccharin . Further pharmaceutical research began in 1917 under Arthur Stoll (1887–1971), who
6800-446: Was identified. The following year, a discharge pipe was shut down after a sinkhole at the corner of Bay Avenue and Vaughn Avenue revealed that it had been leaking. The plant ceased operation in 1996. A follow-up study from the 1996–2000 period indicated that while there were more cancer cases than expected, rates had significantly fallen and the difference was statistically insignificant compared to normal statewide cancer rates. Since 1996,
6885-476: Was imposed a fine of €385 million by the French competition authority on accusations of abusive practices to preserve sales of Lucentis over a cheaper drug. Also in September, BioNTech has leased a large production facility from Novartis to follow all advance demands for its coronavirus vaccine in Europe and sell it to China. In July 2020, Novartis agreed to pay $ 678 million to settle allegations that
6970-639: Was invited to live in the latter's house and teach a course at Harvard. Shortly thereafter, he introduced Leary to LSD. Hollingshead participated in the Concord Prison Experiment with Leary, Ralph Metzner , and others in 1962. For the next few years he worked with psychedelic therapists, and lived at Millbrook, New York with Leary and Richard Alpert (a.k.a. Ram Dass ). He then set up a New York-based project of his own together with Jean Houston , where guided trips were performed and data gathered which, according to Hollingshead's book, formed
7055-428: Was later used for the large scale fermentation of ciclosporin. The immunosuppressive effect of the natural product ciclosporin was discovered on 31 January 1972 in a screening test on immune suppression designed and implemented by Hartmann F. Stähelin at Sandoz. The chemical structure of cyclosporin was determined in 1976, also at Sandoz. The success of the drug candidate ciclosporin in preventing organ rejection
7140-432: Was revived in 2003 when Novartis consolidated its generic drugs businesses into a single subsidiary and named it Sandoz. Novartis divested its agrochemical and genetically modified crops business in 2000 with the spinout of Syngenta in partnership with AstraZeneca , which also divested its agrochemical business. The new company also acquired a series of acquisitions in order to strengthen its core businesses. Novartis
7225-583: Was shown in kidney transplants by R.Y. Calne and colleagues at the University of Cambridge, and in liver transplants performed by Thomas Starzl at the Children's Hospital of Pittsburgh . The first patient, on 9 March 1980, was a 28-year-old woman. In the United States, the Food and Drug Administration (FDA) approved ciclosporin for clinical use in 1983. Thomas Starzl 's 1992 memoir explains through
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