Seek and destroy mission for molecular assassin

University of New South Wales (UNSW) researchers have developed an experimental drug designed to seek out and destroy a 'master' gene implicated in many vascular diseases.

The research is published in the July issue of Nature Biotechnology.

The researchers say the new class of experimental drug has the potential to treat a diverse range of health problems, from inflammation and cancer through to eye and heart disease.

Certain types of skin cancers and blindness due to age-related macular degeneration (AMD) and diabetic retinopathy are likely to be among the first uses for the drug.

The experimental drug has already been shown to be effective on skin cancers in pre-clinical models, in another paper published in July by UNSW Professor Levon Khachigian's team in the journal Oncogene.

"This may be a 'one-size fits all' therapy, because it targets a master regulator gene called c-Jun, which appears to be involved in all of these diseases," Khachigian, a molecular biologist with UNSW's Centre for Vascular Research (CVR), said.

"c-Jun is an important disease-causing gene. It stands out because we don't see much of it in normal tissue but it is highly expressed in diseased blood vessels, eyes, lungs, joints, and in the gut - in any number of areas involving inflammation and aggressive vascular growth. "Our experimental drug, Dz13, is like a secret agent that finds its target, c-Jun, within the cell and destroys it. It is a specific, pre-programmed 'molecular assassin'."

The paper in Nature Biotechnology shows the potential of c-Jun as a drug target in inflammation. It details tests in a variety of pre-clinical models showing how effective Dz13 is in problems such as eye disease and arthritis.

The next phase in the therapy's development would be a trial involving up to 10 people with non-melanoma skin cancers. The tumours would be injected with the drug over an eight-week period.

"If such a trial were successful, it would be a significant development given the high rates of skin cancer and because the main treatment currently is surgical excision, which can cause scarring," Khachigian said.

"Conventional anti-inflammatory drugs are associated with a whole host of side-effects. Our therapeutic may potentially avert some of these."

A third paper using the same technology, but focusing on a different master regulator, Egr-1, has also been published by Khachigian's group in the Journal of Thrombosis and Haemostasis and shows that heart muscle damage is reduced by the drug after a heart attack.