An evidence-based review of natalizumab therapy in the management of Crohn&amp;rsquo;s disease

Edula, Raja G Reddy; Picco, M.F.

doi:10.2147/tcrm.s5550

Cited by 1 publication

(1 citation statement)

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“…The most dramatic effects on binding were seen for the mAbs that target the functional motifs of α4. Of note, a significant obliteration was observed for HP2/1 binding, an antibody that was used as a basis for the development of natalizumab, a clinically approved and widely used drug for the treatment of neurodegenerative disorders such as multiple sclerosis [31] , [32] , and under clinical trials for Crohn's disease and other autoimmune conditions [33] , [34] . Although we have not yet identified a similar polymorphism in human α4, we can envisage a scenario in which particular ITGA4 polymorphisms in humans might negatively impact the efficacy of natalizumab for treating neurological disorders as well as other autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the α4 Integrin of Neotropical Primates: Insights for Binding of Natural Ligands and HIV-1 gp120 to the Human α4β7

et al. 2011

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The α4 integrin subunit associates with β7 and β1 and plays important roles in immune function and cell trafficking. The gut-homing receptor α4β7 has been recently described as a new receptor for HIV. Here, we describe polymorphisms of ITGA4 gene in New World primates (NWP), and tested their impact on the binding to monoclonal antibodies, natural ligands (MAdCAM and VCAM), and several gp120 HIV-1 envelope proteins. Genomic DNA of NWP specimens comprising all genera of the group had their exons 5 and 6 (encoding the region of binding to the ligands studied) analyzed. The polymorphisms found were introduced into an ITGA4 cDNA clone encoding the human α4 subunit. Mutant α4 proteins were co-expressed with β7 and were tested for binding of mAbs, MAdCAM, VCAM and gp120 of HIV-1, which was compared to the wild-type (human) α4. Mutant α4 proteins harboring the K201E/I/N substitution had reduced binding of all ligands tested, including HIV-1 gp120 envelopes. The mAbs found with reduced biding included one from which a clinically-approved drug for the treatment of neurological disorders has been derived. α4 polymorphisms in other primate species may influence outcomes in the development and treatment of infectious and autoimmune diseases in humans and in non-human primates.

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Section: Discussionmentioning

confidence: 99%

Polymorphisms in the α4 Integrin of Neotropical Primates: Insights for Binding of Natural Ligands and HIV-1 gp120 to the Human α4β7

et al. 2011

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show abstract

An evidence-based review of natalizumab therapy in the management of Crohn’s disease

Abstract: Treatment options for Crohn's disease have evolved beyond the early goals of induction and remission and are now more focused on preventing complications by altering the natural history of the disease.

Cited by 1 publication

References 40 publications

Polymorphisms in the α4 Integrin of Neotropical Primates: Insights for Binding of Natural Ligands and HIV-1 gp120 to the Human α4β7

Polymorphisms in the α4 Integrin of Neotropical Primates: Insights for Binding of Natural Ligands and HIV-1 gp120 to the Human α4β7

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