Diabetes: improving wound healing

Diabetes is reaching epidemic levels, with an estimated 2.35 million sufferers in England alone.(1) One of the most distressing complications is poor wound healing. Laboratory tests are underway to find out whether a potential new treatment, called Nexagon (or connexin 43 antisense gel) might promote healing. The long-term hope is to improve the healing of chronic ulcers and thereby prevent the need for amputation.

What's the problem and who does it affect?

The number of people with diabetes is rising dramatically, from an estimated 30 million worldwide in 1985 to a predicted 300 million or more by 2025.(2) There’s no cure for diabetes. It can be treated very successfully, but many people suffer long-term complications.

One of the most troublesome complications is that wounds to the skin can take an extremely long time to heal. Wounds on the feet can be particularly problematic. Diabetes can cause a loss of sensation, meaning people don’t necessarily notice sores developing on their feet. High blood glucose levels and poor blood flow in the foot, also caused by diabetes, can mean the sore becomes infected and an ulcer develops.

Chronic wounds can be life-threatening

Chronic wounds like ulcers can be a serious problem. Every year in the UK, 5,000 people with diabetes have an amputation – that’s 100 people every week.(3) The vast majority of amputations are caused by infected ulcers that simply refuse to heal. Tragically, up to 68% of people die within 5 years of having an amputation.(4)

What is the project trying to achieve?

Can a new gel promote healing of ulcers?

Researchers working on this project have already developed a new treatment for wounds, a gel called Nexagon. Laboratory tests show this gel can speed up healing and reduce scarring in a variety of fresh cuts, and burns, in healthy tissues.

Researchers think the gel might also promote healing in the longer-lasting ulcers suffered by people with diabetes. It works by blocking the production of a protein, called connexin 43, which plays a key role in communication between neighbouring cells. Preliminary data suggests this protein might well be over-produced in wounds of people with diabetes.

In this study, researchers hope to find out more by studying laboratory models of both intact, and wounded, diabetic skin, using powerful microscopes. The team will investigate whether the gel improves wound healing, trying to find the most appropriate dosage and timing of administration.

What are the researchers' credentials?

The project leader, Dr David Becker, is a world expert in communication between neighbouring cells. The group’s lab, in the Centre for Cell and Molecular Dynamics, at UCL, houses extremely sophisticated, world-class microscopy equipment.

The Nexagon gel Dr Becker’s team developed is the first of its kind. By changing the way cells communicate in wounded tissue, the gel speeds up healing whilst reducing inflammation and scar formation.

Dr Becker’s team has all the expertise and facilities needed for a successful study of cell-to-cell communication in diabetes, where it appears to be abnormal. By finding ways to target this abnormal communication, they hope to develop treatments that promote wound healing in diabetes.

Who stands to benefit from this research and how?

Striving to improve wound healing

Researchers expect this project will show whether Nexagon promotes wound healing in diabetic skin in the laboratory. If it does, they plan to move towards clinical trials of the gel as quickly as possible.

The first trials will probably focus on finding out whether the gel can speed up the healing process in diabetics if applied soon after injury. If it can, researchers hope to set up further trials to find out whether the gel might help the one in six people with diabetes who develop the long-lasting, and life-threatening, ulcers on their feet.(4,5)

Foot ulcers are a major drain on NHS resources, being a common cause of admission to hospital for people with diabetes. Improvements in the rate of healing would mean considerable savings.

Benefits to patients would include increased mobility, decreased pain and anxiety, and freedom from the need to see a nurse for daily dressings. It might help stop people with diabetes from having their leg amputated – in the UK, more than one in ten foot ulcers results in an amputation.(3) This could also help save patients’ lives.

References

1. Dr Sue Roberts (National Clinical Director for Diabetes to the Secretary of State for Health). Turning the corner: improving diabetes care. Department of Health, ref 273641, 2006.
2. Diabetes: the cost of diabetes. World Health Organization. Fact Sheet No 236, Revised September 2002.
3. ‘Diabetic Foot Guide’, NHS, National Diabetes Support Team, April 2006.
4. Reiber GE, Boyko EJ, Smith DG. Lower extremity foot ulcers and amputations in diabetes. Chapter 18, p409-28, in Diabetes in America, 2nd Edition, available from the National Diabetes Information Clearinghouse, National Institutes of Health, USA.
5. Lefebvre P (President of the International Diabetes Federation). Amputations linked to diabetes. International Review of Patient Care, Autumn 2005, 24-25.