PROJECT SUMMARY:
Diabetes commonly causes problems with nerves in the hands and feet and limbs of patients. This may be a simple loss of sensation or it can be burning or itching, ranging up to quite intense pain. It appears to be caused by loss of some of the fine nerve fibres near the skin surface. The actual cause of this is unclear, but the nerve fibres seem to be unable to regenerate successfully, once they start to degenerate. The nerve problems can cause very significant suffering for diabetic patients in the long term, and are currently incurable. Existing treatments are aimed at minimising or masking the irritation or pain, rather than treating the underlying problem.
Our research group has been working for some years on a small naturally-occurring protein – metallothionein – which has potent effects on nerve fibres and nerve cells. Metallothionein can induce nerve fibres grown in culture to regenerate when cut. It can also act as a chemical “lure”, attracting regenerating nerve fibres towards its site of administration. We have also shown that metallothionein has potent effects on nerve cell regeneration when injected into the brains of animals which have received an injury – this type of injury in the brain generally does not regenerate.
We therefore hypothesize that metallothionein might help to regenerate nerve fibres in the skin of diabetic patients, both by switching on regeneration (nerve fibre growth) and by directing the fibres towards the site where the metallothionein has been applied (e.g. a region of little or no sensation on the patient’s skin).
To test this hypothesis, we will examine diabetic rats which have the typical loss of nerve fibres in their skin. We will identify regions of nerve fibre loss (with fine fibres which stimulate the skin), apply metallothionein, and then analyze the nerve fibres for signs of regeneration. We will also test the skin of the animals for any signs of a return of sensation. Analysis of which nerve fibres regenerate will throw light on the molecular mechanisms by which metallothionein acts, and upon why the nerve fibres start to degenerate in diabetic patients in the first place. Most importantly, we will be encouraged to develop further synthetic analogues of metallothionein which are suited to topical administration and can be used as a therapy for neuropathy.
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