Stroke - arundic acid
Strokes are a result of blockage or breakage of a blood vessel in or near the brain, interrupting the blood supply.
Strokes are a result of blockage or breakage of a blood vessel in or near the brain, interrupting the blood supply.
Nerve cells within the brain cannot store oxygen and so need a constant supply in order to function, and as they cannot regenerate themselves, once they die they are not replaced. So stroke survivors often suffer severe disability because of the death of and injury to their neurons.
The treatment of stroke has improved in recent years, but there is still a clear clinical need for more effective drugs. One potential new drug is arundic acid, which is being developed by Japanese company Ono Pharmaceutical.1 An increase in biosynthesis of the protein S-100b has been observed in periinfarct-reactive astrocyte brain cells. This induces neuron death by the release of nitric oxide. Arundic acid, formerly referred to as Ono-2506, modulates this activation of the astrocytes, without affecting blood vessels or thrombi. This means that, unlike blood thinning agents, it does not increase the risk of haemorrhage, and it is hoped that it may be effective even if administered several hours after the stroke.
A prospective randomised blinded placebo-controlled Phase I trial has been carried out in 91 patients with ischaemic stroke.2,3 They were given doses ranging from 2 to 12mg/kg an hour, starting within 24h of the cerebral infarction, and continued for seven days. Significant differences in S-100b levels were seen between patients given the active and those given placebo, and significantly more of those given the 8mg/kg dose achieved total functional recovery compared to those given placebo.
Phase II trials are now being carried out in both the US and Japan on an injectable formulation, and it is also being investigated as a potential treatment for amyotrophic lateral sclerosis (motor neurone disease), Parkinson's disease, and Alzheimer's disease.