Natalizumab

Rudick, Richard A.; Polman, Chris H.; Clifford, David B.; Miller, David H.; Steinman, Lawrence

doi:10.1001/jamaneurol.2013.598

Cited by 112 publications

(57 citation statements)

References 68 publications

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“…It prevents the migration of leukocytes across the blood–brain barrier into the CNS by blocking the interaction between α4β1-integrin and VCAM-1 (Rudick and Sandrock, 2004; Ransohoff, 2007; Rudick et al, 2013); moreover, it inhibits the interaction of α4β7-integrin with endothelial MAdCAM-1 and thereby homing of lymphocytes to gastrointestinal lymphoid tissue (Hamann et al, 1994). Studies in patients with MS have shown that natalizumab administration significantly reduced the numbers of total leukocytes, CD4+ T cells, CD8+ T cells, B cells and plasma cells in the cerebrospinal fluid (Stüve et al, 2006).…”

Section: Leukocyte Integrin Blockade In Clinical Usementioning

confidence: 99%

Leukocyte integrins: Role in leukocyte recruitment and as therapeutic targets in inflammatory disease

Mitroulis

Alexaki

Kourtzelis

et al. 2015

Pharmacology & Therapeutics

232

217

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Infection or sterile inflammation triggers site-specific attraction of leukocytes. Leukocyte recruitment is a process comprising several steps orchestrated by adhesion molecules, chemokines, cytokines and endogenous regulatory molecules. Distinct adhesive interactions between endothelial cells and leukocytes and signalling mechanisms contribute to the temporal and spatial fine-tuning of the leukocyte adhesion cascade. Central players in the leukocyte adhesion cascade include the leukocyte adhesion receptors of the β2-integrin family, such as the αLβ2 and αMβ2 integrins, or of the β1-integrin family, such as the α4β1- integrin. Given the central involvement of leukocyte recruitment in different inflammatory and autoimmune diseases, the leukocyte adhesion cascade in general, and leukocyte integrins in particular, represent key therapeutic targets. In this context, the present review focuses on the role of leukocyte integrins in the leukocyte adhesion cascade. Experimental evidence that has implicated leukocyte integrins as targets in animal models of inflammatory disorders, such as experimental autoimmune encephalomyelitis, psoriasis, inflammatory bone loss and inflammatory bowel disease as well as preclinical and clinical therapeutic applications of antibodies that target leukocyte integrins in various inflammatory disorders are presented. Finally, we review recent findings on endogenous inhibitors that modify leukocyte integrin function, which could emerge as promising therapeutic targets.

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Section: Leukocyte Integrin Blockade In Clinical Usementioning

confidence: 99%

Leukocyte integrins: Role in leukocyte recruitment and as therapeutic targets in inflammatory disease

Mitroulis

Alexaki

Kourtzelis

et al. 2015

Pharmacology & Therapeutics

232

217

View full text Add to dashboard Cite

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“…Given the documented changes in activated and memory T cell subsets in people with PD, these drugs could have therapeutic success in limiting development of such T cell populations. The drug, natalizumab has been successful in the treatment of multiple sclerosis [190]. As an antibody against the α4 integrin, this antibody blocks the recruitment of T cells to sites of inflammation.…”

Section: Immunomodulatory Therapies In Pdmentioning

confidence: 99%

The Role of Innate and Adaptive Immunity in Parkinson's Disease

Kannarkat

Boss

Tansey

2013

Journal of Parkinson's Disease

278

201

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In recent years, inflammation has become implicated as a major pathogenic factor in the onset and progression of Parkinson's disease. Understanding the precise role for inflammation in PD will likely lead to understanding of how sporadic disease arises. In vivo evidence for inflammation in PD includes microglial activation, increased expression of inflammatory genes in the periphery and in the central nervous system (CNS), infiltration of peripheral immune cells into the CNS, and altered composition and phenotype of peripheral immune cells. These findings are recapitulated in various animal models of PD and are reviewed herein. Furthermore, we examine the potential relevance of PD-linked genetic mutations to altered immune function and the extent to which environmental exposures that recapitulate these phenotypes, which may lead to sporadic PD through similar mechanisms. Given the implications of immune system involvement on disease progression, we conclude by reviewing the evidence supporting the potential efficacy of immunomodulatory therapies in PD prevention or treatment. There is a clear need for additional research to clarify the role of immunity and inflammation in this chronic, neurodegenerative disease.

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“…Natalizumab (Tysabri®; Biogen, Cambridge, MA, USA) is a humanized monoclonal antibody indicated for relapsing-remitting MS (RRMS) [6] that prevents leukocyte migration into the brain and reduces inflammation in MS patients [7, 8]. Within the United States, natalizumab is also approved for treatment of patients with CD [6]; in CD, natalizumab inhibits leukocyte adhesion and migration into gut tissue [9].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of pregnancy outcomes from the Tysabri® (natalizumab) pregnancy exposure registry: a global, observational, follow-up study

et al. 2016

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BackgroundPatients with multiple sclerosis (MS) or Crohn’s disease (CD) being treated with natalizumab (Tysabri®, Biogen) who are planning to become pregnant or discover they are pregnant after exposure to natalizumab are currently advised to balance the potential benefits and potential risks of exposure when considering treatment options. This study was undertaken to evaluate pregnancy outcomes of women with MS or CD who were exposed to natalizumab at any time within 3 months prior to conception or during pregnancy. A pregnancy registry was created to better understand the effect of natalizumab exposure on pregnancy outcomes.MethodsThe Tysabri Pregnancy Exposure Registry was a global, observational exposure registration and follow-up study. Evaluations included spontaneous abortions (<22 weeks gestational age), fetal losses (≥22 weeks gestational age), ectopic pregnancies, elective or therapeutic terminations, stillbirths, birth defects, and live births. Birth defects were reviewed and coded in accordance with the Metropolitan Atlanta Congenital Defects Program (MACDP) classification of birth defects.ResultsA total of 369 patients with MS and 7 patients with CD were enrolled prospectively, of whom 355 patients (99.4 %; 349 MS and 6 CD) had known pregnancy outcomes (including 8 twin sets). The spontaneous abortion rate was 9.0 % (n = 32; 95 % confidence interval [C. I.], 6.3–12.5 %). An independent advisory committee review determined the major birth defect rate to be 5.05 % (16 of 316 live births + 1 elective abortion; 95 % C. I., 2.9–8.1 %). The mean gestational age of the live-born infants was 38.3 weeks, and the mean birth weight was 3158.3 g.ConclusionsAlthough the overall rate of birth defects was higher than that observed by the MACDP, these registry outcomes showed no specific pattern of malformations that would suggest a drug effect, and the spontaneous abortion rate was consistent with that of the general population.Trial registrationClinicalTrials.gov NCT00472992 (11 May 2007).

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Natalizumab

Cited by 112 publications

References 68 publications

Leukocyte integrins: Role in leukocyte recruitment and as therapeutic targets in inflammatory disease

Leukocyte integrins: Role in leukocyte recruitment and as therapeutic targets in inflammatory disease

The Role of Innate and Adaptive Immunity in Parkinson's Disease

Evaluation of pregnancy outcomes from the Tysabri® (natalizumab) pregnancy exposure registry: a global, observational, follow-up study

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