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Preventing limb amputation

The Vascular Complications Group is working on a new treatment to prevent limb amputation due to cardiovascular disease.

Cardiovascular disease (CVD) affects one in every six Australians – meaning over 4.2 million people and their families have felt its terrible consequences.

The disease can manifest in many ways, including heart attack, stroke and peripheral artery disease (PAD).

In PAD, blood flow to the limbs is reduced due to narrowed arteries. When circulation is cut off, the limb develops gangrene and starts to decay and die. There is no cure for gangrene. The only treatment option is to amputate the affected limb to prevent the gangrene from spreading further in the body.

People with type 2 diabetes are three to four times more likely to develop cardiovascular conditions, including PAD, placing this additional group of 850,000 Australians at risk of limb amputation as well. Shockingly, every three hours in Australia, one person has an arm or leg amputated due to PAD. With one Australian developing diabetes every five minutes, this rate will continue to climb.

In addition, diabetes-related amputations and associated costs place a $875 million burden on the Australian healthcare system every single year.

It’s clear that new treatments to fight PAD and protect people from its devastating consequences are urgently needed.

Our solution

TRAIL (Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand) is a naturally occurring molecule discovered around 25 years ago which was found to kill cancer cells in laboratory experiments, but which is yet to show significant benefit in clinical trials.

We have made a groundbreaking discovery about the mechanisms underlying TRAIL and have shown that it can stimulate the growth of new blood vessels and dramatically improve blood flow to the limbs in animal experiments. This is significant because TRAIL levels are depleted in CVD.

This discovery offers hope of a potential new treatment pathway for PAD. If we could identify a drug that will increase TRAIL levels in people with PAD, so that new blood vessels grew, we could bypass the narrowed arteries and restore blood flow to the limbs. This would help protect the individual with PAD from developing gangrene and amputation.

The next step

In the next phase of our research, we will develop a highly specialised procedure to identify molecules that increase and activate TRAIL signals. We will then use this procedure to screen thousands of molecules which are already listed in approved drug libraries to identify those which can activate TRAIL and which could potentially form the basis of a new treatment for PAD.

We seek funding to kick-start this phase. Funding totalling $100,000 would cover:

  • Salary of Level 2 Research Assistant: $80,000
  • Purchase of drug library: $10,000
  • Consumables: $10,000

The outcome

With the successful completion of our next research phase, we expect to have identified two to three molecules that could potentially be fast-tracked through pre-clinical animal experiments and be trialled as a drug formulation in humans. We could have a better treatment for PAD on the market which would help protect people with PAD from developing gangrene and requiring amputation.

This would not only relieve the financial burden on the stretched Australian healthcare system, with fewer people requiring hospitalisation due to amputation, but also improve the health and quality of life of the thousands of people suffering from PAD.

Project leader

Associate Professor Mary Kavurma

Vascular Complications Group, Lab Head
Read more

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