University of Michigan > A New Tysabri

iBridge is a great resource for entrepreneurs who are looking for technologies to license.  Many premiere universities including Michigan, Columbia, MIT, Penn, and Harvard, participate in the iBridge program.  Launched by the Kauffman Foundation, iBridge “provides a public, centralized source for unbiased information about early stage technologies and inventions”.

Recently, an iBridge post by the Michigan tech transfer office caught my eye.

Inflammation is a fundamental response to tissue injury and invasion of pathogens, but it is detrimental in clinically important inflammatory disorders such as multiple sclerosis and inflammatory bowel disease. Leukocytes are key players in the inflammatory response cascade because of their antimicrobial, secretory, and phagocytic activities. They are recruited to the inflamed tissue by sequential adhesive interactions between leukocytes and the endothelium that are mediated by cell-adhesion molecules (CAMs) on the surface of the interacting cells.

Interactions of cell adhesion molecules (CAM) play central roles in mediating immune and inflammatory responses and understanding the mechanism CAM binding to their ligands is integral to developing therapeutic agents to treat diseases such as multiple sclerosis and inflammatory bowel disease.  MADCAM-1 and VCAM-1 are two CAMs that are tightly regulated by a4b7 integrin, which plays a crucial role in the physiological homing of T cells and monocytes on the intestinal microvasculature.

A team at the University of Michigan have designed a humanized antibody that blocks a4b7 integrin binding to MADCAM-1, which could provide a new therapeutic modality for inflammatory diseases. 

The a4b integrin family might be familiar to some people as this class includes the a4b1 integrin natralizumab, better known as Tysabri.  Natralizumab has wonderful efficacy but also the unintended side effect of making the brain vulnerable to the activation of the JC virus, which can lead to progressive multifocal leukoencephalopathy (PML). 

The Michigan team developed a more specific treatment of inflammatory and autoimmune diseases by targeting an interaction between adhesion molecules preferentially expressed on pathogenic T cells and in chronically infected gut and liver. The inventors used the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), to show previously undocumented expression of the α4-β7 integrin complex and MADCAM-1. This targeted approach to CAM inhibition has great potential to induce  strong efficacy with relatively less side effects when translated to the clinic.