Saturday, May 29, 2010

Life Without a Smile

MDA / Quest 4-3 / Life Without a Smile


by Margaret Wahl

Songs tell us we're never fully dressed without a smile and exhort us to pack up our troubles in our old kit bags and -- smile, smile, smile. Smiling mouths tell us to buy everything from toothpaste and shampoo to diamonds and automobiles, and stylized "smiley faces" peer at us from posters and stickers.

There's more space in the brain devoted to muscle control of the face than to any other part of the body except the hands. And, a part of the brain known as the amygdala has as one of its specific functions the interpretation of other people's facial expressions.

Smiling is considered a milestone in a baby's life, one anxiously awaited by parents. ("Is it a smile, or is it just gas?" they wonder. "Is the baby connected to us yet?")

But, what about people, like many with facioscapulohumeral muscular dystrophy (FSHD), who can't smile? For many with this condition, weakness in the facial muscles makes any facial expression difficult, and smiling is particularly hard.

Paul Topkin of Lakeland, Fla., has his picture taken fairly often, mostly because of his recent fame as a builder of replicas of historic ships that sell for thousands of dollars to individuals and corporations.

Some people might see a photo of the 56-year-old Topkin and think he's a rather grim-looking artist, perhaps in need of treatment for depression. But Topkin has FSHD and, despite a lively sense of humor, he can't smile.

To Read More

Friday, May 21, 2010

DUX4c Is Up-Regulated in FSHD


Facioscapulohumeral muscular dystrophy (FSHD) is a dominant disease linked to contractions of the D4Z4 repeat array in 4q35. We have previously identified a double homeobox gene (DUX4) within each D4Z4 unit that encodes a transcription factor expressed in FSHD but not control myoblasts. DUX4 and its target genes contribute to the global dysregulation of gene expression observed in FSHD. We have now characterized the homologous DUX4c gene mapped 42 kb centromeric of the D4Z4 repeat array. It encodes a 47-kDa protein with a double homeodomain identical to DUX4 but divergent in the carboxyl-terminal region. DUX4c was detected in primary myoblast extracts by Western blot with a specific antiserum, and was induced upon differentiation. The protein was increased about 2-fold in FSHD versus control myotubes but reached 2-10-fold induction in FSHD muscle biopsies. We have shown by Western blot and by a DNA-binding assay that DUX4c over-expression induced the MYF5 myogenic regulator and its DNA-binding activity. DUX4c might stabilize the MYF5 protein as we detected their interaction by co-immunoprecipitation. In keeping with the known role of Myf5 in myoblast accumulation during mouse muscle regeneration DUX4c over-expression activated proliferation of human primary myoblasts and inhibited their differentiation. Altogether, these results suggested that DUX4c could be involved in muscle regeneration and that changes in its expression could contribute to the FSHD pathology.

Read Complete research report

Monday, May 17, 2010

Toolbar for FSH Research

Another way you can help MAKE A DIFFERENCE!

It's the new Pacific Northwest Friends of FSH Research toolbar - once added to IE or Firefox, each time you shop at more than 1,300 stores (from Amazon to Zazzle!) a percentage of your purchase will automatically be donated to Pacific Northwest Friends of FSH Research - at no cost to you (and you may even save money as the toolbar provides coupons and deals as well!).
The toolbar also has a search box and each time you search the Internet, about a penny is donated to Pacific Northwest Friends of FSH Research.

Friday, May 14, 2010

FSHD Review

Natural History

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by progressive muscle weakness involving the face, scapular stabilizers, upper arm, lower leg (peroneal muscles), and hip girdle [Tawil et al 1998]. Asymmetry of limb and/or shoulder weakness is common [Kilmer et al 1995]. Typically, individuals with FSHD become symptomatic in their teens, but age of onset is variable. More than 90% of affected individuals demonstrate findings by age 20 years. Individuals with severe infantile FSHD have muscle weakness at birth. In contrast, some individuals remain asymptomatic throughout their lives. Progression is usually slow and continuous; however, many affected individuals describe a stuttering course with periods of disease inactivity followed by periods of rapid deterioration. Eventually 20% of affected individuals require a wheelchair.

To Read the complete report in Gene Link go to:

Wednesday, May 12, 2010

Neuromuscular Electrical Stimulation Training

Physical Therapy Approach to FSHD

Arch Phys Med Rehabil. 2010 May;91(5):697-702.
Neuromuscular electrical stimulation training: a safe and effective treatment for facioscapulohumeral muscular dystrophy patients.
University of Nice-Sophia Antipolis, Laboratory of Human Motricity, Education, and Health, Faculty of Sports Sciences, Nice Cedex, France.
OBJECTIVE: To investigate the feasibility, safety, and effectiveness of neuromuscular electrical stimulation (NMES) strength training in facioscapulohumeral muscular dystrophy (FSHD) patients.
DESIGN: Uncontrolled before-after trial.
SETTING: Neuromuscular disease center in a university hospital and a private-practice physical therapy office.
PARTICIPANTS: FSHD patients (N=9; 3 women, 6 men; age 55.2+/-10.4y) clinically characterized by shoulder girdle and quadriceps femoris muscle weakness.
INTERVENTIONS: Patients underwent 5 months of strength training with NMES bilaterally applied to the deltoideus, trapezius transversalis, vastus lateralis, and vastus medialis muscles for five 20-minute sessions per week.
MAIN OUTCOME MEASURES: Plasma creatine kinase (CK) activity; scores for pain and fatigue on visual analog scales (VAS), manual muscle testing (MMT), maximal voluntary isometric contraction (MVIC), 6-minute walking tests (6MWT), and self-reported changes in daily living activities.
RESULTS: NMES strength training was well tolerated (CK activity and pain and fatigue scores on VAS were not modified). Most of the muscle functions (shoulder flexion and extension and knee extension) assessed by MMT were significantly increased. MVIC of shoulder flexion and abduction and the 6MWT distance were also improved.
CONCLUSIONS: In FSHD, NMES strength training appears to be safe with positive effects on muscle function, strength, and capacity for daily activities.

Sunday, May 9, 2010

MDA / Quest Extra / Abnormal Activation

MDA / Quest Extra / Abnormal Activation

Abnormal Activation
New findings show abnormally activated parts of a gene called DUX4 may underlie FSH dystrophy

An MDA-supported team of scientists in the United States and the Netherlands has uncovered new leads about the origins of facioscapulohumeral muscular dystrophy (FSHD), a disease whose biochemical underpinnings have proved elusive to scientists despite years of investigation.

Lack of understanding of the mechanisms involved in FSHD has impeded treatment development, a phase of research that generally moves forward after disease mechanisms have been described.

About FSHD

FSHD is a form of muscular dystrophy that preferentially affects the muscles of the face ("facio"), shoulder ("scapulo") and upper arm ("humeral"). Affecting both males and females, it usually begins by age 20 and progresses slowly.

Difficulty smiling and upper-body weakness are typical of FSHD. The development of treatments has been hampered by lack of understanding of the disease process. This new research finding provides important clues to this process.

The genetic cause, a missing stretch of DNA (DNA "deletion") on chromosome 4, has been known since the 1990s. But attempts to pin down the specific effects of the DNA deletion, such as by finding specific genes in or near the region that have been altered by it, has led to more confusion than answers.

About the new findings

The new findings, published in the July issue of Human Molecular Genetics, focus on a gene known as DUX4, located near the end of chromosome 4 in the same region that harbors the FSHD-causing DNA deletion.

MDA supported work done by Sara Winokur at the University of California-Irvine, Silvere van der Maarel at Leiden University Medical Center in the Netherlands, and Galina Filippova at the Fred Hutchinson Cancer Research Center in Seattle. Rabi Tawil, who co-directs the MDA clinic at the University of Rochester (N.Y.) Medical Center, was also on the study team.

The researchers built on many previous studies, many of which have suggested that the loss of a DNA on chromosome 4 releases a molecular brake, activating genes in or near the deletion-containing region that would otherwise be inactive. Much of the focus until now has been on inappropriate activation of a chromosome-4 gene called FRG1.

DUX4 has been previously investigated as a culprit in FSHD, and some researchers found it to be active, whereas others have believed it to be inactive.

The new research supports both positions. DUX4 is for the most part inactive, it seems. However, it now appears that in FSHD-affected cells, pieces of DUX4 DNA are activated. They're transcribed into RNA (the first step a cell takes when making a protein molecule from an activated stretch of DNA) and some of these RNA pieces can then be translated into protein molecules.

One of the protein molecules made from the partially activated DUX4 gene was found to interfere with muscle development in cells in the laboratory. Other protein and RNA molecules from the abnormally activated DUX4 gene could have toxic effects as well, the researchers say. Therefore, any of them have the potential to become targets for therapeutic development.

Meaning for patients

There is no immediate potential for treatment from the new findings. However, if blocking or destroying one or more of the toxic pieces of RNA or protein improves or stabilizes weakness in an animal model of FSHD, a biotechnology company could become interested in developing the concept into a drug for human use. MDA supports this kind of drug development through its MDA Venture Philanthropy program (MVP).

If someone in your family has FSHD, you can help speed research by joining the National Registry of Myotonic Dystrophy & FSHD Patients and Family Members. This registry, supported by the National Institutes of Health and administered by the University of Rochester (N.Y.) Medical Center, connects patients with investigators.