A molecule that kills cancer cells can also save diabetics and heart patients from limb amputation, an Australian-American study shows. Breakthrough work headed by the Heart Research Institute offers up a potential new treatment for people with diabetes who develop cardiovascular disease and have to have limbs removed.
The Heart Research Institute teamed up with scientists from the University of New South Wales in Australia and the University of Minnesota in the USA, to investigate better treatment options for Peripheral artery disease (PAD), a circulatory problem in which narrowed arteries reduce blood flow to the limbs.
Patients commonly have to have limbs amputated when circulation is cut off and the limb starts to die.
The researchers discovered hope with Tumor Necrosis Factor–Related Apoptosis‐Inducing Ligand, or ‘TRAIL’, a naturally-occurring molecule discovered almost 20 years ago for its ability to kill cancer cells. It has been used in several anti-cancer trials since the mid-1990s but is yet to show significant survival benefit.
They found that TRAIL can stimulate blood vessel growth and restore blood flow to the legs of mice, effectively reversing the blood flow blockage in the lower body.
“If given to humans as a new gene therapy, TRAIL could protect diabetics from developing gangrene, and spare them from the amputations they so often have to face,” says Dr Mary Kavurma, senior author of the study published in the Journal of the American Heart Association.
“Such a treatment would allow them to potentially live a longer and more fulfilling life.”
There are an estimated 7 million people living with cardiovascular disease in the UK – 3.5 million men and 3.5 million women. Cardiovascular disease causes more than a quarter (27 per cent) of all deaths in the UK. Current treatments include coronary bypass, angioplasty or surgical amputations, all highly invasive options.
Type-2 diabetics are three to four times more likely to develop cardiovascular conditions including PAD, placing this huge group (3.5 million people in the UK) at risk of limb amputation as well.
“Many diabetic patients with PAD require multiple amputations due to the progression of gangrene,” Dr Kavurma says.
“These complications and treatments place immense stress and hardship on families, making it all the more urgent to develop new and improved therapies,” she said.
The researchers found that when injected directly into the muscle of rodents, the drug can stimulate blood vessel growth and dramatically improve blood flow to the legs.
“We also identified a new mechanistic pathway, describing how TRAIL may do this,” Dr Kavurma says. “This is really exciting as it suggests that we have the beginnings of a new gene therapy that could be injected straight into the muscle of patients, bypassing the blockage with new blood vessels.
On the back of the study’s success, the multidisciplinary team plans to run further tests on mice before moving into clinical trials in PAD patients who have a mild artery blockage in their legs.
“Unfortunately it’s still too soon to say when the average person in the UK will get access to this treatment as a matter of course,” the specialist in vascular complications says.
“But from what we can tell at this stage, when they do it will be a far superior treatment options to the surgery and amputations they must currently contend with.”
To view the paper, click the link: http://jaha.ahajournals.org/content/4/11/e002527.long