Atherid Therapeutics: Juliana Hamzah and Shirley Jansen hope future vascular drug will rid world of disease

Two Perth researchers are leading the world in the fight to cure vascular disease after discovering a way to dissolve the plaque that clogs arteries. Associate Professor Juliana Hamzah and Professor Shirley Jansen have been on the journey to find a cure for atherosclerosis for 10 years and counting. It’s a blood vessel disease that causes a build-up of cholesterol and other fats in the walls of the arteries, making them narrower and more prone to blockage. This in turn increases the risk of stroke, heart attack, kidney failure and more. Their efforts have so far culminated in $750,000 in funding to accelerate the production of the drug candidate — Atherid — that could offer the cure. But when Associate Professor Hamzah first made the discovery that would kick off years of development and testing, she thought it was a mistake. “The results were exciting but really we were scratching our heads,” she said. Associate Professor Hamzah has led the targeted drug delivery, imaging and therapy laboratory at the Harry Perkins Institute of Medical Research since 2013. “My program is about drug development, so I have the expertise to make proteins and change their molecules. The idea is that if we inject a protein, it can circulate throughout the body, but it binds to diseased tissue,” she said. ATH01, or Atherid, was originally developed to treat stiff cancers, like tumours. “Because (cancer tissue) is very, very tight and stiff, blood vessels in the cancer collapse. So drug delivery in stiff cancer is difficult,” Associate Professor Hamzah said. “What we did was use ATH01 to open the blood vessels.” Associate Professor Hamzah’s research background in cardiovascular disease then sparked an idea that would lead her and Professor Jansen to founding Atherid Therapeutics. The environments in which cancer and cardiovascular disease grow are similar because they’re the “wound that never heals”, she said. Testing that theory led to more than half the plaque in a clogged arterial wall being dissolved. “We saw more than 50 per cent removal of the plaque. That was very exciting, but almost too good to be true,” Associate Professor Hamzah said. “So we actually spent six years trying to reproduce (these results) . . . it’s not something that you can just whip up . . . do it today and then tomorrow you can get it.” That’s when her partnership with Professor Jansen formed. “The driving force behind the understanding of how we can apply this drug to patients, this is through (Professor Jansen’s) insight and medical experience,” Associate Professor Hamzah said. As head of vascular surgery at Sir Charles Gairdner Hospital, Professor Jansen has seen more of the devastating effects of vascular disease than most ever will. “I’ve been a vascular surgeon for over 20 years and spend my life dealing with dramatic complications of atherosclerosis or plaque build-up in arteries, as well as other vascular pathologies,” she said. “The treatments we offer . . . really just moves the disease out of the way or bypasses it.” While traditional methods alleviate symptoms, Atherid is geared towards removing the problem altogether. “This was really exciting to be able to really embrace the concept of curing the underlying problem,” Professor Jansen said. “When we saw the initial results, we couldn’t really believe them, because it was quite dramatic.” Atherid combines two molecules, a natural “messenger protein” and a “homing” molecule that targets the plaque in the artery walls. “We like these molecules because they can modulate a lot of biological responses,” Associate Professor Hamzah said. It then triggers the process of breaking down the build-up of fats and clearing the plaque, returning blood flow to normal and reducing the risk of blockages or organ damage. “This drug activates a collective metabolic pathway in the cells that helps break down the stored cholesterol molecules . . . in the cells,” Associate Professor Hamzah said. “In a way it’s like a fat burner, and that releases in the form of energy.” It’s a short treatment, with results evident around 10 weeks later. “What we’re aiming for is to visualise how this treatment can basically regress patients’ plaque,” Associate Professor Hamzah said. Despite being in the early stages of development, they receive daily requests for the potentially life-changing drug from all over the world. It’s because the burden of peripheral arterial disease is enormous, encompassing disease in 200 million people globally. Patients with its most severe form, known as chronic limb-threatening ischaemia, are at risk of losing their legs. “Their survival is worse than that of most cancers. So this is something that’s really, really poorly understood,” Professor Jansen said. “The term ‘peripheral arterial disease’ is unhelpful as a lay person. What is that? What does that actually mean? It just means the non-heart, non-brain arteries, really.” The pair are excited by the possibility of changing disease outcomes — even curing them — but they remain measured and aware of the long road to reaching such a milestone. The success rate of such a drug is about two per cent, Associate Professor Hamzah said. “One drug — from discovery to the clinic — takes $1 billion, on average,” she said. The next step on the journey is finding a manufacturer that meets the Therapeutic Goods Administration’s good manufacturing practices requirement, a stringent set of rules that allow safe, high-quality medicines to be made at scale. “We need a new game-changer — we’re hopeful this is it,” Professor Jansen said.