Metabolic adds pain compound to drug roster

Melbourne biotech Metabolic Pharmaceuticals (ASX:MBP) is looking for a fast and pain-free path to market for the latest addition to its IP portfolio: a potent peptide from cone-shell venom that shows great promise in the treatment of chronic, intractable nerve pain.

Metabolic has acquired exclusive, worldwide rights to commercialise the compound, ACV1, from a Melbourne University research team led by Assoc Prof Bruce Livett.

Metabolic CEO Chris Belyea said current estimates indicated that around 1 per cent of the world's population suffered from some form of neuropathic pain, which originated in abnormal nerve activity. The most common forms include chronic pain resulting from physical trauma, particularly back injuries, diabetic neuropathy, and shingles.

Livett's team has already put the ACV1 compound, from the Australian cone snail Conus victoriae, through advanced efficacy testing, and confirmed its "profound analgesic properties."

The venoms of cone snails contain rich cocktails of peptide toxins that paralyse and kill their prey. Collectors prize their beautifully patterned shells, and at least one species, the geographer's cone snail, is capable of killing incautious humans with its paralysing venom.

The peptides in each species' venom are neurotoxins that rapidly paralyse and immobilise prey, through a variety of selective activities against range of receptors in the peripheral nervous system.

Livett's research team found that the ACV1 peptide from C. victoriae has novel, highly selective activity against a particular receptor sub-type in the neuronal nicotinic acetylcholine receptor family

A number of conotoxin-derived peptides have been shown to be powerful analgesics, but most have adverse side-effects. The only commercial analgesic derived from cone snail venom, Elan Pharmaceuticals' Ziconotide, elevates blood pressure when administered intravenously, requiring it to be injected directly into the spinal cord.

Livett's team found that ACV1 was a very potent analgesic, but without side-effects when given intravenously -- properties that, if confirmed in clinical trials, could make it a superior option to Ziconotide.

According to Metabolic, it provides substantial pain relief in animal models of nerve pain. Neuropathic pain -- chronic nerve pain that arises from the abnormal activity of pain-sensing nerves -- resists treatment by the even the most powerful conventional analgesics. It can arise after physical trauma, or major surgery.

Unlike opiate painkillers like morphine, conotoxin analgesics do not become addictive with prolonged use. Chronic, high doses of conventional analgesics like aspirin and codeine can also have adverse side-effects, including digestive-tract damage.

Neuropathic pain is the pain category with the greatest need for improved drugs. Metabolic says the global market for analgesics for neuropathic pain is estimated at several billion dollars a year, so an effective new therapy could become a blockbuster drug, rivaling the selective anti-inflammatory analgesic Celebrex, now widely used to treat arthritis.

According to Metabolic, Livett's team has found "interesting indications" in animal models of nerve injury that ACV1 also accelerates the functional recovery of nerves that have suffered restriction or compression injuries- the cause of painful disorders such as sciatica and chronic back pain in humans.

Because Livett's team has already taken ACV1 through efficacy trials, Metabolic has advanced it to number two on its list of lead compounds, behind its promising new anti-obesity candidate molecule AOD9604.

Metabolic said Livett's team had amassed a large amount of efficacy data that would allow ACV1 to be moved into a pre-clinical toxicity study program early next year.

The company said the lack of effective treatments for neuropathic pain meant an effective, safe therapy would be rapidly taken up by doctors, who are currently limited to prescribing anti-convulsants and anti-depressants, which have only limited and temporary effiicacy.

Belyea said the current global market for an effective therapy for a novel analgesic for neuropathic pain is estimated at US$2.2 billion, rising to US$10 billion by 2010.