Researchers in the Comparative Neuromuscular Diseases Laboratory at the Royal Veterinary College (RVC) have discovered an answer to the long un-solved question about the molecular mechanism which underpins a common form of ‘tying up’. This breakthrough is enabling the team at the RVC to work towards improved treatments and management for this disorder, to improve the welfare of affected horses.
This form of ‘tying up’, scientifically known as Type 1 Polysaccharide Storage Myopathy (PSSM1), is a common condition that damages equine muscle tissue. The genetic cause of PSSM1 was discovered in 2008, at the University of Minnesota. Researchers found that affected animals have a mutation of a key enzyme (glycogen synthase) involved in energy metabolism in muscle and increased storage of glycogen and an abnormal type of polysaccharide (a form of carbohydrate). Horses that carry the mutation are prone to ‘tying up’ and other muscle problems such as weakness. Until now, no-one knew the precise mechanism by which the mutation caused increased enzyme activity in muscles.
Dr Charlotte Maile and Professor Richard Piercy at the RVC led an international team of scientists from the University of Copenhagen, University of Minnesota, Indiana University School of Medicine and Liverpool John Moore’s University, to discover the answer.
The mutation in the enzyme leads to a change in the enzyme’s structure which leaves it permanently active, so it cannot be switched off. This hyperactivity of mutant equine enzyme explains the increased muscle glycogen and the accumulation of polysaccharide that leads to the clinical problems in affected horses. This significant step forward in the understanding of PSSM1 might lead to the development of novel treatments for this debilitating disease and it explains why some forms of treatment might be ineffective. RVC researchers are now working towards improved treatments and management of this disorder.
Dr Charlotte Maile, Postdoctoral Research Fellow, said: “PSSM1 is a very common disease, especially in some breeds. Finally we know the reason why these horses store excessive glycogen and polysaccharide in their muscles. Our goal now is to use this information in designing new treatments and management strategies”
Professor Richard Piercy, Professor of Comparative Neuromuscular Disease, said: “Managing horses that tie-up is hard, and some recommended treatments work poorly in some animals. By revealing the precise mechanism for this form of tying up, our work should make a real difference. Our hope is that by targeting specific approaches to the problem, rather than a ‘one treatment fits all’ – horse welfare will be improved allowing them to get back to exercise, which has to be good for the horse and their owner ”.
The RVC’s work was partly funded by the Petplan Charitable Trust and the Morris Animal Foundation.
The article can be read here: A highly prevalent equine glycogen storage disease is explained by constitutive activation of a mutant glycogen synthase. Biochim Biophys Acta. 2016 Aug 31. pii: S0304-4165(16)30321-X. doi: 10.1016/j.bbagen.2016.08.021.
