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Anti-adhesion therapies
1Inflammation Discovery Research, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA02140, USA. dsimmons@wyeth.com
Current Opinion in Pharmacology
|June 16, 2005
Summary
Cell adhesion molecules, like LFA-1, are crucial in inflammation and targeted by new therapies. Recent drug approvals show promise but also highlight safety challenges in therapeutic development.
Area of Science:
- Immunology and Pharmacology
- Structural Biology
Background:
- Cell adhesion molecules (CAMs) mediate inflammatory processes, making them key targets for novel therapeutics.
- Advances in basic research provide structural insights into CAM function, particularly integrin-ligand interactions.
Purpose of the Study:
- To review recent progress in understanding cell adhesion molecule function and therapeutic development.
- To highlight structural insights and clinical advancements in targeting CAMs for inflammatory diseases.
Main Methods:
- Analysis of published co-crystal structures of integrin-ligand complexes.
- Review of clinical development of anti-adhesion therapeutics targeting specific CAMs.
Main Results:
- Detailed structural understanding of integrin-ligand interactions, including LFA-1 with ICAM-1.
- Successful clinical approval of efalizumab (targeting LFA-1) and natalizumab (targeting VLA-4).
- Natalizumab withdrawal due to safety concerns, impacting the therapeutic landscape.
Conclusions:
- Structural biology advances inform the development of integrin-targeting drugs.
- Clinical success of anti-adhesion therapies is demonstrated, but safety monitoring is critical.
- The field shows significant promise for novel therapeutics targeting inflammatory processes via cell adhesion molecules.