Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0010346 (Crohn's disease)
 21,615 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

OraSense Ltd (a joint venture between Isis Pharmaceuticals Inc and Elan Corp) is developing ISIS-104838, an antisense oligonucleotide specific for TNF alpha mRNA, as an inhibitor of TNF alpha synthesis. The compound is being developed for the potential treatment of inflammatory diseases such as rheumatoid arthritis, Crohn's disease and psoriasis. This antisense oligonucleotide is currently undergoing phase II clinical trials for RA and Crohn's disease.
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PMID:Technology evaluation: ISIS-104838, OraSense. 1266 75

Natalizumab is a humanized monoclonal antibody to alpha 4 beta 1 integrin (VLA-4) currently under development by Elan and Biogen for the treatment of Crohn's disease and multiple sclerosis. Phase II trials in both indications have been completed, and by December 2002 phase III trials in Crohn's disease and multiple sclerosis had been initiated.
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PMID:Natalizumab. Elan/Biogen. 1475 75

Natalizumab [AN 100226, anti-alpha4 integrin monoclonal antibody, Antegren] is a humanised monoclonal antibody that blocks alpha4beta1 integrin-mediated leukocyte migration. Natalizumab is in phase III trials for the treatment of multiple sclerosis in North America and the UK, and for the treatment of Crohn's disease also in the UK. It may have potential in the treatment of other immune-related inflammatory disease. Elan Corporation intends to examine the potential of natalizumab in rheumatoid arthritis and ulcerative colitis. 4beta1 integrin on circulating leukocytes binds to vascular cell adhesion molecule-1, which is expressed at high levels in the blood vessels in the CNS during exacerbations of multiple sclerosis. This allows leukocytes expressing alpha4beta1 integrin (very late antigen-4) to move from the peripheral blood into the CNS. Inflammatory proteins and other factors released from lymphocytes in the brain lead to the progression of symptoms. A limitation of natalizumab is that it must be injected and cannot be administered orally. Scientists have transformed the large anti-alpha4 monoclonal antibody into much smaller, drug-like molecules suitable for oral administration. Protein Design Labs has granted a worldwide nonexclusive licence under its antibody humanisation patents to Elan Pharmaceuticals for natalizumab. Biogen Inc. has entered into an agreement with Elan for a worldwide exclusive collaboration to develop, manufacture and commercialise natalizumab for multiple sclerosis and Crohn's disease and rheumatoid arthritis. Development of natalizumab is also being funded, in part, by Axogen (acquired by Elan in 1999). In November 2003, Biogen and IDEC Pharmaceuticals merged to form Biogen Idec. Elan repurchased royalty rights on a package of products, including natalizumab, from Autoimmune Disease Research Company. Elan and Genzyme Transgenics Corporation signed an agreement to produce natalizumab in GTC's genetically engineered goats, which will express the compound in their milk. Genzyme Transgenics Corporation changed its name to GTC Biotherapeutics in June 2002; it is no longer a subsidiary of Genzyme Corporation. Following discussions with the US FDA, Elan completed enrolment in a second phase III trial, involving approximately 420 patients with Crohn's disease. This Evaluation of Natalizumab as Continuous Therapy-2 (ENACT-2) trial evaluated the effect of natalizumab on duration of response and remission in patients with Crohn's disease. In January 2004, Elan Corporation and Biogen Idec announced that the phase III, ENACT-2 maintenance trial of natalizumab in Crohn's disease met the primary endpoint of maintenance of response. Elan and Biogen Idec will discuss these data with regulatory authorities in both the US and Europe and determine the appropriate path forward for natalizumab in Crohn's disease. An NDA for Antegren in Crohn's disease was expected to be filed at the end of 2003; however, due to failing to meet the primary endpoint in the induction trial, Elan is unable to predict when and if a regulatory filing will be made. Earlier, on 23 January 2001, the Wall Street Journal reported that the Biogen CEO expects Antegren to become a blockbuster drug, with sales of at least $US1 billion. He also predicted that Antegren could be on the market as early as 2003 for the indication of Crohn's disease and in 2004 for multiple sclerosis. The Journal stated that Biogen is under pressure to develop new drugs since its flagship product Avonex will be losing its US Orphan Drug Act protection in 2003. Antegren has a different mechanism to that of Avonex and could be used either alone or as a combination therapy.
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PMID:Natalizumab: AN 100226, anti-4alpha integrin monoclonal antibody. 1529 71

AN-100226 (Antegren), a humanized monoclonal antibody (MAb) directed against the alpha4beta1 integrin (VLA-4) expressed on leukocytes, is under development by Athena Neurosciences as a potential treatment of exacerbations in multiple sclerosis (MS). VLA-4 specifically binds to VCAM-1, a ligand present on brain endothelial cells which is a potential mediator of autoimmune disorders, leading to MS [222518]. Phase II trials in 70 patients with MS in the UK were assessed over a 12-week period. Antegren significantly reduced new brain lesions [275424]. In two separate pilot studies involving a total of 40 patients suffering from Crohn's disease or ulcerative colitis, treatment with Antegrin was well-tolerated and efficacious. Interim analysis of phase II data has indicated promising results [179966,276967]. Antegren is claimed in the associated patent, WO-09519790. VLA-4 itself and monoclonal antibodies for the integrin were first described in a patent (EP-00330506) by the Dana-Farber Cancer Institute. In April 1998, Protein Design Labs (PDL) granted a worldwide, non-exclusive license for Antegren under its antibody humanization patents, to a subsidiary of Elan [286198].
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PMID:Antegren Athena Neurosciences Inc. 1846 35

Natalizumab (Tysabri, formerly known as Antegren, Elan Pharmaceuticals [Elan; San Francisco, CA, USA] and Biogen Idec [Biogen; Cambridge, MA, USA]) is a humanized monoclonal antibody against alpha4 integrin, which inhibits leukocyte adhesion and migration into inflamed tissue. The drug has been shown to be more efficacious than placebo in inducing response and maintaining remission in moderate-to-severe Crohn's disease. There have been reports of progressive multifocal leukoencephalopathy after treatment with natalizumab in Crohn's disease and multiple sclerosis. It has been otherwise well tolerated, although it is associated with an increased risk of infections, especially influenza and influenza-like illness. The drug is not approved in Europe for the treatment of Crohn's disease, but it is approved in the USA for the treatment of both multiple sclerosis and moderate-to-severe Crohn's disease. Owing to the risk of progressive multifocal leukoencephalopathy, it can only be given under the TOUCH program, which is a special restricted distribution program available only to prescribers, infusion centers, pharmacies associated with infusion sites and patients who are enrolled in the program.
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PMID:Natalizumab for the treatment of Crohn's disease. 2059 22

Natalizumab (Tysabri, Biogen Idec and Elan Pharmaceuticals) is a monoclonal antibody approved for use in patients with relapsing multiple sclerosis (MS) as well as moderate to severe Crohn's disease. We report the first case of a patient with a history of MS, on monthly natalizumab, who developed HSV-2 meningitis. We discuss the mechanism of action of natalizumab and review what is known about the reactivation of herpes infection in association with this medication. The question of herpes simplex virus (HSV) and varicella zoster virus (VZV) prophylaxis for patients is raised.
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PMID:Natalizumab and HSV meningitis. 2148 35