Neuroprotection in stroke; a slow burner.
One of the real surprises of medical school is coming to terms with the protracted nature of medical research. Developing a robust drug which passes appropriate quality and safety standards is increasingly likely to tip-toe over the decade mark onwards.
Within Neurology, arguably the most troublesome of clinic trials has revolved around finding a group of neuroprotective agents which tick all the boxes. Neuroprotection works on the principal that neuronal tissue may be salvaged from an ischaemic event by endowing it with a greater resilience to the effects of hypoxia.
While neuroprotective agents offer a tantalizing holy grail of a lower risk, lower resource alternative to thrombolytics, the development process has been dogged by setbacks..... To the tune of over 1000 unsuccessful potential treatments. Most of which have been nipped in the bud by the jump from cellular and rodent models to human trials by an unwanted side effects profile or ineffectiveness.
NA-1, is a neuroprotective agent that has previously been shown to be efficacious in a primate model of stroke. It works by disrupting the neurotoxic pathways of NMDA glutamate receptors and imbuing cells with a greater tolerance to hypoxia. A recent Lancet Neurology paper followed a phase II trial of individuals undergoing endovascular intracranial aneurysm repair. Participants were randomized to receive either intraoperative NA-1 or a saline control. Up to 90% of individuals undergoing this procedure show evidence of small embolic iatrogenic stroke on diffusion weighted MRI. So the study group was a very appropriate target to put it mildly.
Individuals receiving NA-1 were significantly less likely to have experienced new brain infarctions (OR 0.53 CL 0.38-74) on DW MRI then controls. More so, rather conspicuously, the authors reported no serious adverse effects of the study drug, a promising finding that if genuine warrants a larger trial. However the drug's administration soley to individuals who were anaesthetised may limit its study in the near future to invasive treatments carrying a risk of brain injury rather than community admitted patients with ischaemic stroke.
For the moment the clock keeps ticking…