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Massive MicroRNA Scan Uncovers Leads To Treating Muscle Degeneration

Date:
October 22, 2007
Source:
Children's Hospital Boston
Summary:
An increasing number of genes have been linked to muscular dystrophy and related disorders that cause muscle weakness and wasting, but it's still largely unknown how these genes cause disease, and, more importantly, how to translate the discoveries into treatments. A wealth of new clues about how muscle function is regulated has been found by analyzing microRNAs -- tiny bits of code that govern gene expression.

Researchers have discovered the first microRNAs -- tiny bits of code that regulate gene activity -- linked to each of 10 major degenerative muscular disorders, opening doors to new treatments and a better biological understanding of these debilitating, poorly understood, often untreatable diseases. The study, to be published online by the Proceedings of the National Academy of Sciences, was led by Iris Eisenberg, PhD, of the Program in Genomics at Children's Hospital Boston. Louis Kunkel, PhD, director of the Program in Genomics and an investigator with the Howard Hughes Medical Institute, was senior investigator.

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The disorders include the muscular dystrophies (Duchenne muscular dystrophy, Becker muscular dystrophy, limb girdle muscular dystrophies, Miyoshi myopathy, and fascioscapulohumeral muscular dystrophy); the congenital myopathies (nemaline myopathy); and the inflammatory myopathies (polymyositis, dermatomyositis, and inclusion body myositis). While past studies have linked them with an increasing number of genes, it's still largely unknown how these genes cause muscle weakness and wasting, and, more importantly, how to translate the discoveries into treatments.

For instance, most muscular dystrophies begin with a known mutation in a "master gene," leading to damaged or absent proteins in muscle cells. In Duchenne and Becker muscular dystrophies, the absent protein is dystrophin, as Kunkel himself discovered in 1987. Its absence causes muscle tissue to weaken and rupture, and the tissue becomes progressively nonfunctional through inflammatory attacks and other damaging events that aren't fully understood.

"The initial mutations do not explain why patients are losing their muscle so fast," says Eisenberg. "There are still many unknown genes involved in these processes, as well as in the inflammatory processes taking place in the damaged muscle tissue."

She and Kunkel believe microRNAs may help provide the missing genetic links. Their team analyzed muscle tissue from patients with each of the ten muscular disorders, discovering that 185 microRNAs are either too abundant or too scarce in wasting muscle, compared with healthy muscle.

Discovered in humans only in the past decade, microRNAs are already known to regulate major processes in the body. Therefore, Eisenberg believes microRNAs may be involved in orchestrating the tissue death, inflammatory response and other major degenerative processes in the affected muscle tissue. The researchers used bioinformatics to uncover a list of genes the microRNAs may act on, and now plan to find which microRNAs and genes actually underlie these processes.

The findings raise the possibility of slowing muscle loss by targeting the microRNAs that control these "cascades" of damaging events. This approach is more efficient than targeting individual genes.

The team also defined the abnormal microRNA "signatures" that correspond to each of the ten wasting diseases. They hope these will shed light on the genes and disease mechanisms involved in the most poorly understood and least treatable of the degenerative disorders, such as inclusion body myositis.

"At this point, it's very theoretical, but it's possible," says Eisenberg.

The study was funded by the Howard Hughes Medical Institute and also by the National Center for Research Resources, the Associazione Amici del Centro Dino Ferrari, the Telethon Project, the Eurobiobank Project, the Muscular Dystrophy Association, the National Institutes of Health, the Lee and Penny Anderson Family Foundation, and the Joshua Frase Foundation.


Story Source:

The above story is based on materials provided by Children's Hospital Boston. Note: Materials may be edited for content and length.


Cite This Page:

Children's Hospital Boston. "Massive MicroRNA Scan Uncovers Leads To Treating Muscle Degeneration." ScienceDaily. ScienceDaily, 22 October 2007. <www.sciencedaily.com/releases/2007/10/071017112223.htm>.
Children's Hospital Boston. (2007, October 22). Massive MicroRNA Scan Uncovers Leads To Treating Muscle Degeneration. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2007/10/071017112223.htm
Children's Hospital Boston. "Massive MicroRNA Scan Uncovers Leads To Treating Muscle Degeneration." ScienceDaily. www.sciencedaily.com/releases/2007/10/071017112223.htm (accessed November 27, 2014).

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