Cure for floppy baby syndrome is in the heart

A Perth research team has cured congenital myopathy in mice, representing 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, characterised by a mutation in the muscle protein, actin, where babies are born without the ability to use their muscles. Severe cases render children paralysed and many die before their first birthday.

Head of the neuromuscular disorders laboratory at the West Australian Institute of Medical Research (WAIMR), Professor Nigel Laing, 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.

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, 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.

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.”

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.