Drug Discovery Opinion

DDO Limited – Consultancy for Biotech and Pharma

May 28 2009

Heart Muscle Protein Rescues Mice with ‘Floppy Baby’ Syndrome

Posted by SR in News, tags: genetic linkage

Floppy Baby Syndrome encompasses a number of incurable genetic diseases that cause severe muscle weakness. In one form of the disease, mutations occur in the ACTA1 gene which encodes the skeletal muscle protein, alpha actin. Most babies born with these mutations are almost completely paralysed and die within their first year but a team of Australian scientists identified a number of less severely affected children who were found to have cardiac actin expressed abnormally in skeletal muscle. In the early foetus, cardiac actin is the most abundant form of the protein in both heart and skeletal muscle but, during development, production of skeletal actin increases until it becomes the dominant form in skeletal muscle. Although the switch occurs in all higher vertebrates, it is not clear why it occurs, or why it occurs only in skeletal muscle.

Mice lacking the ACTA1 gene die within nine days of birth but the team have now shown that if the mice are crossed with transgenic mice expressing ACTC at high levels in skeletal muscle cells the pups survive much longer. ACTC encodes the heart muscle protein, alpha cardiac actin, and almost all of the mice with this gene survived for more than three months and some for more than two years. Although their individual muscle fibres were slightly weaker, their overall muscle strength and locomotive performance were comparable with those of wild type mice. The study demonstrates that cardiac actin is sufficiently similar to skeletal actin to produce adequate muscle function and the team hope that ACTC reactivation might provide an approach for the treatment of diseases caused by ACTA1 mutations. The team are exploring the effects of existing medicines to see whether any of them can ‘switch on’ the ACTC gene in skeletal muscle.

The study is published in the Journal of Cell Biology.

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