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West Aussie research breakthrough offers new insight and treatment options for rigid spine syndrome
West Australian researchers have made a breakthrough medical discovery in the fight against a rare genetic muscle disorder.
Professor Gina Ravenscroft, head of the Rare Disease Genetics and Functional Genomics group at the Harry Perkins Institute of Medical Research, and Lein Dofash, PhD student at the institute and University of Western Australia Medical School, identified a new genetic cause of rigid spine syndrome.
It's a rare muscle disorder that usually presents at birth or in infancy, causing spinal stiffness, muscle weakness and breathing difficulties in children.
Most cases are linked to mutations in the SELENON gene, but the latest research found mutations in another gene, HMGCS1.
It plays a role in the mevalonate pathway, which is important for muscle function, with HMGCS1 variants causing muscle weakness.
The researchers found mutations in five patients from four families with links to spinal rigidity, scoliosis and respiratory issues.
'HMGCS1-related myopathy is a recessive disorder, in all the families,' Professor Ravenscroft said.
It means the children with rigid spine syndrome inherited one mutation of the HMGCS1 gene from each healthy parent who doesn't have the disease.
They then teamed up with Monash University's Dr Lee Miles and Professor Robert Bryson-Richardson, who are experts in modelling human muscle diseases in the zebrafish, to confirm the finding.
'Zebrafish are an excellent model to study muscle diseases since young zebrafish are see-through and this allows visualisation of the skeletal muscle (which makes up the bulk of the fish tail),' Professor Ravenscroft said.
'Because of the evolutionary conservation between humans and fish, we can model many human diseases in zebrafish in a timely and cost-efficient manner.'
It also makes them ideal candidates for testing potential treatments for diseases.
The researchers supplemented the fish with mevalonic acid, an important compound in the mevalonate pathway, and found it helped lessen the symptoms of rigid spine syndrome.
The significant findings, published in neurology journal Brain, present a new pathway for treatment of the rare disease.
'If we could secure production of clinical-grade mevalonolactone (mevalonic acid), this could potentially be administered on compassionate grounds to patients with HMGCS1-related myopathy,' Professor Ravenscroft said.
'The next step is to identify further patients with HMGCS1-related myopathy to better understand the range of variants that cause disease and the range of clinical presentations that are caused by variants in HMGCS1.'
