Written by Laura Glitsos Wednesday, 10 June 2009 00:00
A PERTH research team has cured congenital myopathy in mice, in a massive leap towards improving the lives of children suffering from the debilitating muscle disease.
Congenital myopathy, or ‘floppy baby syndrome’, is an incurable genetic disorder where babies are born without the ability to use their muscles.
Severe cases render children paralysed and many die before their first birthday.
The condition is characterised by a mutation in the muscle protein, actin (whereas other muscular diseases such as dystrophy are characterised by a degeneration of muscle fibres).
Head of the neuromuscular disorders laboratory at the West Australian Institute of Medical Research (WAIMR) Professor Nigel Laing has led the research for 20 years with support and funding from WAIMR, the National Health and Medical Research Council, the US and French Muscular Dystrophy Associations and Perth based company, Molecular Discovery Systems.
Prof Laing and the team were responsible for identifying defects in the skeletal muscle actin gene, ACTA1, in 1999.
“In your muscles you have thick filaments and thin filaments, when your muscles contract, the thick and thin slide past each other,” Prof Laing says.
“The main protein in thin filaments is actin, and myosin in the thick filaments.
“We can imagine myosin like a little oar.
“So I think of muscles contracting like 300 little oarsmen on each thick filament, like Charlton Heston in the galleys when you want muscles to contract, the little oarsmen get to work. The oar reaches out and grabs hold of the actin and pulls it past.”
As actin exists in the heart but is switched off before birth, Prof Laing and his team wondered if skeletal muscle actin could be replaced with heart actin.
To test this hypothesis Perth scientist Dr Kristen Nowak worked in Oxford to make transgenic mice, which would express heart actin in skeletal muscles after birth while US researcher Dr Jim Lasard made skeletal muscle knockout mice, with two copies of the defective actin gene.
The two sets of mice were transported to Perth where they were interbred, with their next generation free of the disease.
Prof Laing says the next step is finding a way to maintain the expression of heart actin in the skeletal muscle of children.
“The best solution would be to find a drug to do this, so we are currently researching a drug library to perhaps find a something that has an unknown side effect.”
Prof Laing says there are even patients who have no skeletal actin, but for an unknown reason have managed to maintain heart actin.
With each case based on individual gene mutation, the team is setting up a database of actin mutations found around the world.
Fiona Holmes is the mother of a 3 year old boy, Flynn, who suffers from congenital myopathy and she says the most important aspect of caring for a child born with floppy baby syndrome is to maintain a positive attitude.
“Also, it’s really important to start physiotherapy straight away,” she says.
“While it’s not painful, he can’t do a lot of other things most children can.”
