Metabolic releases data on neuropathic pain drug

A preclinical trial of Metabolic Pharmaceuticals' (ASX:MBP) conotoxin peptide painkiller hints that if it makes it to the clinic, it could provide a health bonus for patients suffering chronic neuropathic pain.

The 16-amino acid peptide, alpha-conotoxin, one of a rich cocktail of peptide components in the venom of the Australian marine cone shell Conus victoriae, has confirmed its ability to deliver relief in a rodent model of neuropathic pain.

But David Kenley, Metabolic's corporate development vice president, said alpha conotoxin also appears to have longer-lived beneficial effects after initial administration, suggesting it may induce the self-repair mechanisms of inflamed nerves.

The peptide, delivered by subcutaneous injection, competitively blocks nicotinic acetylcholine receptors to provide relief from chronic neuropathic pain.

The peptide, ACV1, has a relatively brief half-life in the patient's system - somewhere between 30 minutes to three hours, but Kenley said it appears to exert a residual effect. Treated animals did not fall back to the baseline level of pain as measured in a placebo group.

"It makes us think there's some nerve repair going on," he said. "We need to work out what is going on, but instead of repeated daily dosing, patients might only need a weekly top-up after the initial reaction."

Chronic neuropathic pain due to diabetes or nerve injury is one of modern medicine's most intractable problems. Metabolic's conotoxin already has a major advantage over the only cone-shell toxin commercialised to date, Ziconotide, from Irish biopharma Elan Pharmaceuticals

Safety requires Ziconotide to be injected directly into the patient's spinal cord; subcutaneous or intravenous injection can cause the patient's blood pressure and heart rate to plummet dangerously.

Kenley said any leakage of intrathecally injected contoxin from the spinal cord into the tissues or general circulation can result in unpleasant side effects, particularly if higher doses are used to quell severe neuropathic pain.

The pre-clinical trial indicated that Metabolic's conotoxin is free of such problems - it can be injected at up to 100 times the standard therapeutic dose without serious side effects.

The global market for chronic neuropathic pain is estimated at several billion dollars a year; an effective, safe alternative to current analgesics and anti-inflammatory drugs could become a blockbuster drug. In addition to relieving neuropathic pain in diabetics - a US$1 billion market in its own right - it may also be useful for the neuropathic pain of shingles, a common sequel to infection by Herpes zoster, the chicken pox virus.

The pre-clinical trial results should see the drug enter Phase I/II clinical trials in human volunteers in Australia next month, according to Kenley, depending on the company receiving ethics approval for the trial.

Kenley said it was possible, if the drug confirms its promise in human clinical trials, that the company may moved to develop a stabilised, oral form of the peptide or a synthetic analogue, to avoid the inconvenience of subcutaneous or intramuscular injections.