Prof Merlin Thomas

Diabetes researchers have set up a commercial venture to develop new anti-inflammatory therapies based on the concept of modulating the receptor for advanced glycation end-products (RAGE).

RAGE Biotech is an Australian company aiming to develop new therapies to treat conditions such as diabetes, atherosclerosis and lung disease based on RAGE research by clinicians such as Professor Merlin Thomas of Monash University’s Biochemistry of Diabetes Complications Laboratory.

Professor Thomas says that RAGE is a key mediator of chronic inflammatory and immune responses, and targeting it has been shown to have potential in managing conditions such as COPD, cystic fibrosis and neurogenerative conditions as well as the complications of diabetes and atherosclerosis

“Often it’s not easy to turn inflammation down without disrupting pathways needed for good health. But RAGE only turns up when things are going wrong, which makes it such a great target,” he says.

With funding support from JDRF an Diabetes Australia, Professor Thomas’s Monash group have previously shown that a new pathway by which RAGE can be transactivated by the angiotensin receptor with which it forms a complex. This pathway does not rely on extracellular signalling and likely represents the major way that RAGE is activated.

“Mice lacking RAGE are protected against atherosclerosis associated with diabetes. So we gave them back just the inside part of RAGE and this was enough to restore their sensitivity to diabetic complications,” said Professor Thomas.

Using this knowledge, the researchers then developed a selective inhibitor of the inner tail of RAGE, which was able to block inflammation just as well as RAGE deletion.

RAGE Biotech will test two novel approaches to modulate RAGE in collaboration with Professor Kevin Pfleger at Harry Perkins Institute of Medical Research and UWA Professor and Professor Steve Wilton of Murdoch University.