A novel therapeutic for perennial ryegrass toxicosis

Perennial Ryegrass Toxicosis (PRGT) is a clinical syndrome of herbivores in southern regions of Australia and New Zealand grazing pasture with a high proportion of perennial ryegrass. To date no clinically applicable therapeutic has been available to treat clinical cases of PRGT or to prevent disease. PRGT is a complex toxicity with multiple alkaloids involved. Disease presentations range from subclinical productivity losses to a severe neurological syndrome with ataxia, tremor, recumbency and occasionally death. Lolitrem B, the primary toxin responsible for neurological signs, is thought to block calcium activated potassium channels (BK Channels). In the brain this will have a number of effects; generally it will increase neuronal instability. In the cerebellum however the overall effect is to reduce neuronal outputs. As the cerebellum is involved in regulating movement the effect of intoxication is for movement to become less regulated and more exaggerated (cerebellar ataxia) or the classical “ryegrass staggers” presentation. This presentation considers the use of bromide, an accepted therapy for epilepsy in small animals and humans, as a treatment for PRGT and evaluates therapeutic efficacy within murine and ovine models of Perennial Ryegrass Toxicosis (PRGT). Trials demonstrate that bromide is effective at reducing lolitrem B induced tremor and ataxia. Because of its limited side effects, high oral bioavailability, high safety margin and low cost, bromide is a good potential on-farm therapy for PRGT.