DUX4 Protein Not Unique to FSHD-Affected Muscles

New research reveals full-length DUX4 protein can be produced in the muscles of people without FSHD, contradicting previous evidence placing it only in FSHD-affected tissue

Article Highlights:
  • Production of full-length DUX4 protein has been proposed as a source of muscle abnormalities in facioscapulohumeral muscular dystrophy (FSHD).
  • New research supported in part by MDA now shows full-length DUX4 also can be produced in unaffected relatives of people with FSHD.
  • The investigators suggest that a search be made for factors that modify the level of DUX4 production or its function; they say these could become targets for new therapies.
by Rachel Wellington on August 10, 2012 - 6:00am

Researchers supported in part by MDA have recently found evidence that production of the full-length version of a protein known as DUX4 — previously associated exclusively with facioscapulohumeral muscular dystrophy (FSHD) — also can occur in people who don't have the disease.

Full-length DUX4 protein was discovered in muscle precursor cells and muscle biopsy samples from people with FSHD and their unaffected relatives, prompting investigators to conclude that the presence of full-length DUX4 protein in muscle fibers is necessary, but not sufficient, to cause the disease.

The researchers published their findings online July 13, 2012, in Human Molecular Genetics (abstract available at no charge). MDA supported study team members Jeffrey Miller and Charles Emerson, both at Boston Biomedical Research Institute in Watertown, Mass.

Identifying 'modifiers' of DUX4 production may provide leads

The study suggests that production of full-length DUX4 may play a role in FSHD, as previously reported, but that it is not the only factor in the generation of the disease.

The investigators suggest that other factors — as-yet-unidentified "modifiers" that influence the level or function of DUX4 protein — may determine whether or not full-length DUX4 has a harmful effect on muscle fibers.

Identifying these modifiers, they say, could provide new therapeutic targets at which to aim therapies for FSHD.

In May 2012, researchers supported in part by MDA proposed that an upstream molecular "switch" may modify the activity level of several genes and therefore the level of several proteins, such as DUX4, in FSHD.

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