Prima subsidiary claims arthritis treatment find

Prima BioMed (ASX:PRR) subsidiary Arthron believes it has found a new way of blocking the inflammatory reaction responsible for the crippling autoimmune disease rheumatoid arthritis.

A research team at Melbourne's Austin Research Institute, led by Arthron's chief scientific officer Prof Mark Hogarth, has confirmed that activation of the company's lead therapeutic target, the Fc receptor, triggers the inflammatory cascade that erodes the collagen-rich cartilage that cushions the joints, causing rheumatoid arthritis.

Hogarth said Fc receptors on the surface of infection-fighting macrophages were the docking sites for antibody-antigen complexes -- the receptor is activated when the 'stem' of the Y-shaped antibody plugs into it. Activation of the receptor causes the macrophage to secrete TNF-Alpha, the potent intracellular signalling molecule that triggers the inflammatory attack.

Arthron has developed small synthetic molecules that inhibit the Fc receptor, blocking TNF-Alpha's inflammatory signal at its source. Hogarth said current monoclonal antibody (Mab) therapeutics like Genentech's Embrel, Centocor's Remicade, and Abbott's Humira bind TNF-Alpha, preventing other immune-system cells from receiving its inflammatory signal. Arthron's experimental compounds block the signal at source, he said.

Several drug companies, including Sydney firm Peptech, are reportedly working on second-generation TNF-Alpha blockers based on single-domain antibodies, which promise improved efficacy.

Because Arthron's approach intervenes higher in the inflammatory process, it could also prevent the TNF-Alpha signal from triggering the release of other damaging molecules, according to Hogarth.

He said the advantage of blocking the Fc receptor with small synthetic molecules was that the drugs could be delivered orally, in tablets. Current Mab therapeutics have to be injected to avoid breakdown in the digestive tract.

Arthron has been experimenting with its Fc blockers to confirm that they can prevent immune-system cells releasing TNF-Alpha.

Hogarth said drugs that block the Fc receptor might also be useful in treating other disorders involving antibody-antigen complexes -- most notably, the debilitating autoimmune disorder lupus erythematosus, which predominantly affects women.

Strong IP position

Prima said Arthron had a "very strong" IP position covering both the Fc receptor and the small molecules that target it, so it should be able to avoid the patent disputes swirling around Mab therapeutics.

Both Centocor and Abbott are now declining to pay royalties to Peptech, which has a master patent covering molecules that exploit the TNF-Alpha signalling system.

Current Mab-based therapies block all TNF-Alpha signalling, and a minority of patients suffer adverse side-effects. The Arthron compounds only block TNF-Alpha signals from macrophages, leaving other TNF-Alpha signalling pathways intact. They thus avoid the side effects reported by a small number of rheumatoid arthritis patients on Mab therapy.

Arthron said it was currently in discussions with a several companies to co-develop and license the technology, securing access to additional expertise and resources to develop a marketable drug for testing in human clinical trials.

The company said it was confident that its intellectual property and technical package created an opportunity for "a very significant new therapeutic for rheumatoid arthritis".