Neuren extends US partnership

Preclinical trials of Auckland biopharma Neuren's (ASX:NEU latest neuroprotectant, NNZ-2566, have convinced the US Army's Walter Reed Research Institute in Washington to back a clinical trial of the new drug in brain-trauma patients.

Early trials in a rat model of traumatic brain injury (TBI) developed by WWRI researchers showed it reduced neurological deficits in the wake of injury by 50 per cent.

NNZ-2566 is a stabilised tripeptide, a cousin of Neuren's lead compound Glypromate, which is heading for a phase II trial later this year, after successful phase I trials in Australia.

Under their agreement, Walter Reed has funded half the cost of preclinical research, and will fund half the cost of the human clinical trials, in return for the right to use NNZ-2566 in the US military. Neuren retains all future commercial rights outside the US military.

The latest trial administered the drug over a longer period. It confirmed and trumped the previous result, finding a 70 per cent reduction in neurological deficits after brain injury.

Walter Reed researchers have developed a novel model that uses an early clinical marker that predicts the outcome of traumatic brain injuries. The marker will allow earlier and more cost-effective prediction.

Neuren CEO David Clarke said NNZ-2566 had two advantages over Glypromate: although it is a peptide, the stabilized form can be administered orally, and it has a longer half life in the patient's system.

The drug works by modulating the activity of glial cells -- microglia, astrocytes and oligodendrocytes -- that comprise 80 per per cent of all brain cells. Clarke said it down-regulates microglia, and up-regulates astrocytes.

Glial cells physically support and protect neurons, by secreting healing molecules, and providing immune defences against infection, but in the wake of traumatic brain injuries, begin to secrete excitotoxins, such as glutamate, and inflammatory factors, triggering necrosis and apoptosis

Clarke said NNZ-2566, orally administered, enters the bloodstream and can cross the blood-brain barrier to protect neurons against inflammation.

In addition to traumatic brain injury, Clarke said NNZ-2566 may also be useful in preventing inflammation-caused cognitive deficits after major surgery, especially heart-bypass surgery. Two out of 10 patients suffer brain inflammation after major surgery, as inflammatory factors released into the bloodstream reach the brain.

While both Glypromate and NNZ-2655 are both highly neuroprotective, Clarke said Glypromate's therapeutic 'window' is limited to within 7 to 11 hours of brain injury; NNZ-2655 provides protection out to 24 hours.