BioWorld International Correspondent
DUBLIN, Ireland - A trio of scientists at Trinity College in Dublin teamed up with an Australian biotechnology entrepreneur to establish a new start-up, Opsona Ltd., which aims to extend basic research on microbial-host interactions into the discovery and development of new anti-inflammatory drugs.
The founding team comprises Luke O'Neill and Kingston Mills, both professors of biochemistry at Trinity; Dermot Kelleher, head of clinical medicine at Trinity and a consulting physician at St. James's Hospital in Dublin; and CEO Mark Heffernan, who relocated to Ireland having previously been involved in a number of ventures in his native Australia.
Several U.S. companies are attempting to boost Toll-like receptor (TLR) activity in order to prime the immune system against infection. Opsona is taking the opposite tack, looking for molecules that dampen excessive immunological activity by acting on TLR signal-transduction pathways.
It is starting with a portfolio of seven patents, including filings covering three bacterial and two viral proteins that modulate the inflammation response. O'Neill's team focuses on the signals that switch on and off Toll-like receptors, the class of transmembrane proteins expressed by immune cells that act as molecular sensors of bacterial, viral and parasitic infection and as activators of the innate immune response. O'Neill is a leader in the field, having identified in 2001 a protein called Mal as a signal transducer for TLR-4. That work was published in the Sept. 6, 2001, issue of Nature.
The group's most recent research appears in the April 2004 issue of Nature Immunology, in a paper titled "ST2 is an inhibitor of interleukin-1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance." O'Neill had encountered ST2, a protein that exhibited anti-inflammatory activity, during a sabbatical spent at Millennium Pharmaceuticals Inc., of Cambridge, Mass., several years ago.
"Several labs discovered ST2 in the nineties, [but] nobody knew what it did," he told BioWorld International.
O'Neill and collaborator Foo Liew at the University of Glasgow in Scotland have now shown that the protein's anti-inflammatory effect is mediated via Type I interleukin-1 receptor and TLR-4. Knockout mice deficient in the gene encoding ST2 were highly sensitive to bacterial infection.
"They drop like flies with just a sniff of bacteria," O'Neill said. His group aims to probe that pathway further to find new targets and new proteins with therapeutic potential. It previously identified two proteins encoded by vaccinia virus that disrupt interleukin-1 and TLR-4 signaling. Kingston Mills' group has made similar findings from studying bacterial modulation of the host immune response.
Opsona is focusing on three indications initially: arthritis, inflammatory bowel disease and multiple sclerosis, O'Neill said. Some of the proteins it already has identified have therapeutic potential as biopharmaceuticals, he said, but they could encounter delivery problems. The company also aims to forge partnerships to gain access to medicinal chemistry and high-throughput screening facilities to find small molecules with similar activities.
Opsona was formally established in the past month, but it already has received offers of investment from both Irish and UK venture capital funds. It hopes to raise funds by the summer.
"We need to raise about €5 million initially," O'Neill said.