[…] Consortium and Research Planning Meetings, held in Boston on October 5-6, 2015, brought together over 100 investigators, including leaders in FSHD research and many industry sponsors, to discuss advances made […]
International workshop spotlights progress in facioscapulohumeral muscular dystrophy research
Drug Development Pipeline
[…] looks promising, a company may file an investigational new drug (IND) application with the FDA seeking permission to begin clinical trials in humans. The drug must then go through several trial […]
For your eyes only
[…] promising, a company may file an investigational new drug (IND) application with the FDA seeking permission to begin clinical trials in humans. The drug must then go through several trial […]
2020 Festive Evening of Song
[…] the FSHD Society The FSHD Society Festive Evening Concert Committee will miss seeing you in person this year. We invite you to enjoy a stay-at-home concert, nestled in your favorite […]
From the Wayback Machine, 2010
[…] treatments.” 1. Lemmers et al. “A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy,” Science, published online August 19, 2010. About the FSH Society’s Role in the Science Paper Breakthrough The FSH Society is a 501(c) (3) non-profit patient-led research, education and advocacy organization, founded in 1991. The Society frequently testifies before Congress on the research needs in FSHD. It has funded $2.3 million in $30,000-45,000 a year fellowships to more than five dozen researchers in 11 years, leading to well over a hundred publications in top tier journals. Researcher(s) that published this Science paper have been recipients of FSH Society support and also serve as members of the FSH Society Scientific Advisory Board. Both the first and last authors, Drs. Richard Lemmers and Silvere van der Maarel began their careers in FSHD research as recipients of the prestigious FSH Society Marjorie Bronfman fellowship awards. The FSH Society has provided the Leiden team and many of their partners with funds to support early phases of their work. The FSH Society is a small non-profit with a very dedicated and gifted group of scientific advisors, headed by Prof. David E. Housman, Massachusetts Institute of Technology, and along with its board of directors comprised mainly of patients and with the generous support of thousands of affected FSHD families and family foundations, the Society has helped to solve the mechanism causing FSHD. It has carefully raised funds and targeted many areas of research needed to be examined in FSHD and layered in the foundation for discovery.” The FSH Society has funded many other projects with researchers around the globe who have published on FSHD in recent years; Drs. Jane Hewitt, Peter Jones, Ryan Wuebbles, Michael Kyba, Darko Bosnakovski, and Sara Winokur. All of these findings and papers along with the current breakthrough paper provide the context in which how to approach treating FSHD becomes apparent. This truly demonstrates the effectiveness of patient driven and disease focused organizations. The FSH Society helps the DHHS NIH FSHD patient registry and existing DHHS NIH Sen. Paul D. Wellstone FSHD Cooperative Research Center at the Boston Biomedical Research Institute. The Society is composed of a board of directors of affected persons or family members and has over 4,000 members. Accessing the Paper at Science Online @ ScienceXpress Science Express provides electronic publication of selected Science papers in advance of print. Some editorial changes may occur between the online version and the final printed version. See paper at ScienceXpress Publication ahead of print @ http://www.sciencemag.org/sciencexpress/recent.dtl , or by clicking here. A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy Richard J.L.F. Lemmers1, Patrick J. van der Vliet1, Rinse Klooster1, Sabrina Sacconi2, Pilar Camaño3,4, Johannes G. Dauwerse1, Lauren Snider5, Kirsten R. Straasheijm1, Gert Jan van Ommen1, George W. Padberg6, Daniel G. Miller7, Stephen J. Tapscott5, Rabi Tawil8, Rune R. Frants1, Silvère M. van der Maarel1,* 1. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands 2. Centre de reference pour les maladies Neuromusculaires and CNRS UMR6543, Nice University, Nice, France 3. Department of Neurosciences, BioDonostia Health Research Institute, Hospital Donostia, San Sebastián, Spain 4. CIBERNED, Instituto de Salud Carlos III, Spain 5. Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 6. Department of Neurology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands 7. Department of Pediatrics, University of Washington, Seattle, WA, USA 8. Department of Neurology, University of Rochester Medical Center, NY, USA *To whom correspondence should be addressed. E-mail: maarel@lumc.nl Abstract: Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy in adults that is foremost characterized by progressive wasting of muscles in the upper body. FSHD is associated with contraction of D4Z4 macrosatellite repeats on chromosome 4q35 but this contraction is pathogenic only in certain “permissive” chromosomal backgrounds. Here we show that FSHD patients carry specific single nucleotide polymorphisms (SNPs) in the chromosomal region distal to the last D4Z4 repeat. This FSHD-predisposing configuration creates a canonical polyadenylation signal for transcripts derived from DUX4, a double homeobox gene of unknown function that straddles the last repeat unit and the adjacent sequence. Transfection studies revealed that DUX4 transcripts are efficiently polyadenylated and are more stable when expressed from permissive chromosomes. These findings Lemmers et al 2 suggest that FSHD arises through a toxic gain of function attributable to the stabilized distal DUX4 transcript. A Note on the Origins of this Research Richard Lemmers’ work on the allelic variants was supported by the FSH Society Marjorie Bronfman Fellowship Award, 2005-2009. Both the first and last authors, Drs. Silvere van der Maarel and Richard Lemmers have been the recipients of the prestigious FSH Society Marjorie Bronfman fellowship awards. FSH Society Marjorie Bronfman Post-Doctoral Research Fellowship Grant: FSHS-MGBF-010 Researcher: Richard Lemmers, MSc., Ph.D.* Institution: Leiden University Medical Center Leiden, THE NETHERLANDS Project Title: “Refinement of the FSHD critical region on 4qA chromosomes.” $35,000 6/15/2005 – 6/14/2006 Year 1 $35,000 6/15/2006 – 6/14/2007 Year 2 $35,000 2/15/2008 – 2/14/2009 Year 3 Goal: FSHD is the third most common myopathy, with an autosomal dominant mode of inheritance. FSHD is caused by contraction of the polymorphic D4Z4 repeat in the subtelomere of chromosome 4q and the exact pathogenic mechanism is still unclear. An identical and equally polymorphic D4Z4 repeat is localized on chromosome 10, but this has never been associated with FSHD. Our approach of detailed characterization of FSHD alleles and translating these observations to disease mechanisms has provided robust mechanistic insight in FSHD pathogenesis over the past years, including the mechanism of mitotic D4Z4 instability (Lemmers et al. 2004a) and the recognition of a bi-allelic 4qter variation (designated 4qA and 4qB) of which only the 4qA allele is associated with FSHD (Lemmers et al. 2002). Moreover, our laboratory provided direct evidence for a chromatin modification associated with the contraction of D4Z4 repeats by demonstrating hypomethylation of D4Z4 in FSHD alleles (van Overveld et al. 2003). Through our expertise in pulsed-field gel electrophoresis (PFGE)-based FSHD allele characterization, we have become the international reference center for FSHD diagnosis with on average 50 referrals of atypical FSHD patients each year and culminating in a database of>l000 patient and control genotypes for D4Z4 alleles on chromosomes 4 and 10. Our PFGE-based […]