Podcast: Stephen Tapscott Discusses Role of DUX4 in FSHD

An 11½-minute interview with researcher Stephen Tapscott explores recent findings about the molecular basis of facioscapulohumeral MD

Stephen Tapscott, a former MDA grantee who has served on the Association's Scientific Advisory Committee, explains what DUX4 findings may mean to the FSHD community.
Article Highlights:
  • A podcast featuring researcher Stephen Tapscott discusses recent findings regarding DUX4, a protein that is inappropriately expressed in skeletal muscle in FSHD.
  • DUX4 interferes with many biochemical processes and appears to inhibit the survival and regeneration of skeletal muscle fibers.
  • In the podcast, Tapscott explains why targeting DUX4 and its downstream effects is a promising therapeutic avenue for the treatment of FSHD.
by Quest Staff on February 2, 2012 - 4:55pm

A protein called DUX4, inappropriately produced ("expressed") in skeletal muscle fibers, is emerging as a major factor in facioscapulohumeral muscular dystrophy (FSHD).

In FSHD-affected muscles, full-length DUX4 protein disrupts numerous biochemical pathways that normally would help muscle cells survive, mature and develop specialized roles.

MDA medical and science editor Margaret Wahl recently interviewed Stephen Tapscott, a neurologist and molecular geneticist at the Fred Hutchinson Cancer Research Center in Seattle, about the DUX4 findings and what they may mean for the FSHD community.

The conversation with Tapscott, a former MDA grantee who has served on MDA's Scientific Advisory Committee, is available as an 11½-minute podcast.

Tapscott describes how a mutation on chromosome 4, in which repeated sequences of DNA are deleted, was identified two decades ago as the root cause of FSHD. Since then, many research groups have tried to identify the mechanism by which this deletion leads to loss of muscle tissue in FSHD.

Misregulation of the DUX4 gene and inappropriate expression of the DUX4 protein were proposed early on as possible causes of FSHD, says Tapscott, but until recently, the technology wasn't sufficient to demonstrate their involvement.

It's now clear that the loss of some of the repeated DNA units on chromosome 4 causes the expression of the DUX4 protein in skeletal muscle tissue, where it's not normally expressed.

The presence of DUX4 in skeletal muscle tissue may cause the death of muscle cells via a cell death program known as apoptosis. It also may cause the immune system to attack muscle fibers, and activate proteins that block normal muscle regeneration.

Scientists now have a good road map for therapeutic development in FSHD, says Tapscott, either through blocking DUX4 itself or interfering with its downstream effects.

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