Sheep gene may hold clue to muscular dystrophy cure
It may also assist in the search for a cure for Duchenne muscular dystrophy in humans.McArdle's disease is typified by the deficiency of an enzyme in muscle which is involved in glycogen metabolism. The disease induces muscular pain and fatigue and can often lead to severe muscle weakness.Murdoch researchers recently received two grants worth more than half-a-million dollars from the Muscular Dystrophy Association of North America to carry out their work into McArdle's disease.One of the grants will be used to support a study which will attempt to insert a normal gene into the muscle of the affected sheep. The other grant will be used to try and "switch on" an alternative gene, which will fulfil the role of the defective gene."As far as we know, no-one else has yet tried gene therapy with McArdle's disease," said Emeritus Professor John Howell of Murdoch University's Division of Veterinary and Biomedical Sciences."McArdle's is an inherited disease in which a single gene has gone wrong."In theory, if we can insert a normal gene into the animal and have it produce the missing enzyme, we will have a cure which can be applied to the disease in humans."
First described in humans in 1951, and in Charolais cattle in 1995, McArdle's disease was found to occur in Merino sheep in Western Australia by Dr Jeremy Allen of the State Department of Agriculture.The gene deficit responsible for the disease in sheep was subsequently characterised by Murdoch Veterinary School Honours student Peiling Tan in 1996, while working under the supervision of Murdoch's Associate Professor Clive Huxtable and Associate Professor Nigel Laing of the Australian Neuromuscular Research Institute.The findings led to the establishment of a breeding flock of sheep at the Murdoch University Veterinary Farm.Working with ANRI researchers Dr Sue Fletcher, Dr Steve Wilton, and Adjunct Associate Professor Nigel Laing, and with Dr Teresa Collins of Murdoch University, the research team's first step was to attempt to insert the gene into the tissues of the sheep using a modified human adevovirus."This virus is produced in Montreal, Canada by Dr George Karpati's team at the Neuromuscular Institute," said Professor Howell."It uses a human gene provided by Dr Salvatore DiMauro of the Columbia-Presbyterian Medical Centre, New York. After undergoing further processing at ANRI, the gene is finally ready for the trials at Murdoch University."Professor Howell said two trials had already been carried out with definite expressions of the gene obtained in the sheep's muscles."We have produced the human enzyme in the muscles of animals that did not formerly possess that enzyme," said Professor Howell.Associate Professor Nigel Laing said that of the three varieties of the enzyme found in young and adult sheep, one particular enzyme, found only in the foetus, disappeared soon after the animal was born."Our most recent area of research explores the possibility of switching this gene back on again permanently, and this is the strategy of the second of the grants," said Professor Laing."The results of the trials in the sheep model of the human disease will help considerably in providing the basic information that is required before any trials in humans are allowed."The results of the trials in animals will provide the basis for trials in humans."However, before authorities will allow clinical trials in humans involving gene therapy, an enormous amount of information about the effects of gene therapy on animals is required. Associate Professor Laing added that since the discovery of McArdle's disease in Western Australia, the Murdoch/ANRI research group had developed tests to both identify the naturally-occurring disease and eradicate it. Further information
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Emeritus Professor John Howell Division of Veterinary and Biomedical Sciences Telephone (08) 9360 2477 email jhowell@central.murdoch.edu.au |