On February 13, Canadian biotech, Reserverlogix announced that facioscapulohumeral muscular dystrophy (FSHD) is one of two new indications it is pursuing involving its lead drug, apabetalone (RVX-208) which inhibits bromodomain and extra-terminal (BET) epigenetic readers. It mentioned research conducted at Saint Louis University demonstrating apabetalone mediated modulation of important targets in FSHD. The FSH Society funded seminal seed-funds to Dr. Fran Sverdrup at Saint Louis University starting in 2014 to conduct pilot research to study BET proteins as therapeutic targets in FSHD. It is still early days with respect to this research. Dr. Fran Sverdrup in response to inquiries he has received following the Resverlogix press release, along with the desire to start managing patient expectations about the status of BET inhibitors as a potential therapy for FSHD and research required to validate a candidate drug as an effective treatment, has put together the following Q&A to inform our readers about the status of BET inhibitors.
What are BET inhibitors? BET inhibitors are a class of drugs with anti-inflammatory and anti-cancer properties. Although no BET inhibitors are yet approved for use in the US or internationally, there are several clinical trials ongoing in the areas of cancer and cardiovascular disease. These drugs bind to and inhibit Bromodomain and Extra-Terminal motif (BET) proteins BRD2, BRD3, BRD4, and BRDT. Since BET proteins generally bind to active or “open” chromatin and turn on nearby genes, BET inhibitors act to suppress (turn off) genes that are over-expressed in disease settings. Continue reading
Our eye-catching T-Shirts, totes and mugs feature the Bach 2 Bowie logo from the Ghostly Gala, our annual Los Angeles-based event to raise awareness and funds to fight FSH muscular dystrophy, one of the most common hereditary muscle-weakening diseases. Just as music unites us, so does our care and concern for the health and well being of individuals and families affected by FSHD. Net proceeds support the FSH Society.
Deadline March 30. A minimum of 25 orders must be placed to trigger production. Your credit card will not be charged until then.
Order your Bach 2 Bowie items here.
Frank Kolakowski and Manuel Gomez, FSHD advocates extraordinaire, were on hand to represent FSH muscular dystrophy at this year’s National Institutes of Health Rare Disease Day event. Thank you!
Barbara A. Chin (1945-2016)
We at the FSH Society were deeply moved and inspired to receive yesterday a magnificent bequest of $50,000 from the Barbara A. Chin Trust. This gift will enable the Society to fund work that Barbara cared deeply about: education and support for people with FSH muscular dystrophy, like herself and her late son Jimmie, and research toward treatments and a cure.
Barbara and her husband Jim, who serves on the Society’s Board of Directors, have supported the Society not only financially but through countless hours of volunteer service. Barbara changed the lives of many patients and families through her peer counseling. The entire FSHD community owes her so much.
Barbara’s bequest helps ensure that future generations will enjoy lives free of the burdens of this disease. Individuals and families even of modest means can leave a powerful legacy by including the FSH Society in their will or estate plans. Continue reading
First report from the FSH Society’s tissue donation registry
by Kelly Jackson, Fulcrum Therapeutics, Cambridge, Massachusetts
At Fulcrum Therapeutics, human tissue serves as one of the most basic yet essential tools available to help in efforts to develop new medicines to treat FSHD and other genetic diseases.
Human biospecimens have long served as a foundation for the development of precision medicines. By deeply analyzing human tissue at the cellular level, researchers gain indispensable insights into how a disease progresses, which may open the door to new treatment strategies. These insights also enable the development of personalized molecular tools that are used to evaluate the safety and efficacy of novel therapeutics as they move through human clinical trials. Continue reading
Video caption: These mice are siblings and genetically identical. In the one on the right, we turned DUX4 “on”, while in the one on the left, the DUX4 gene remained “off”. FSHD mice have a slow and unsteady gait caused by weakened muscles. You may also notice a hunched back, which is also a sign of muscles being too weak to support the skeleton properly. We are using these animals to test therapies that inhibit DUX4. Credit to Carlee Giesige, a PhD student in the lab, for the video and for characterizing these mice.
by Scott Harper, PhD, Columbus, Ohio
Mouse models of disease are important tools for developing therapies. During the past decade or so, several attempts have been made to generate FSHD mouse models that express the DUX4 gene in their chromosomes.
Although these models were designed logically, the animals were difficult to produce, and they did not show the muscle weakness and damage seen in humans. These first models also suggested that it was difficult to make mice expressing human DUX4, because the gene was toxic and incompatible with normal mouse development.
We concluded that if we wanted to make a DUX4 mouse, we would have to tightly control when and where it could be turned “on,” and began working to generate a new FSHD mouse model in 2009. After many difficulties, we finally successfully produced a model in which DUX4 could be turned on only in muscles. Continue reading
by Peter Jones, PhD, and Takako Jones, PhD, University of Nevada, Reno
The aberrant expression of the DUX4 primate retrotransposon is the key mediator of all forms of FSHD. Thus, the DUX4-fl mRNA and protein are prime targets for therapeutic intervention.
Our laboratory at the University of Nevada, Reno School of Medicine reports the successful generation and free distribution of a viable, fertile, and highly tunable phenotypic FSHD-like transgenic mouse model based on the controlled expression of DUX4. This mouse, referred to as FLExDUX4 (or FLExD), is now available from The Jackson Laboratory as B6(Cg)-Gt(ROSA)26Sortm1.1(DUX4*)/Plj/J, catalog #028710 (https://www.jax.org/strain/028710).
H&E staining shows severe muscle pathology in gastrocnemius muscles of ACTA1-MCM, FLExD severe FSHD-like model mice (center) compared with ACTA1-MCM healthy control mice (left). DUX4 immunostaining (right) shows mosaic expression and the nuclear localization of DUX4 protein in gastrocnemius muscle after TMX induction. Figure courtesy of Jones laboratory.
About 12 members of the Sacramento FSH Society Support Group met at Mimi’s Café on February 8th. We had a new attendee who moved from Monterey and had never met another person with FSHD until a few years ago when she met the daughter’s of the FSH Society president. Chris Ford was in attendance and announced that she was now on the board of directors for the FSH Society and would like to serve as a conduit between the FSH Society and our support group. Continue reading
Last November, the FSH Society invited its members to participate in a survey designed to gauge what members understand about patient registries and for researchers to gain insight into what kind of information patients expect to learn from registries. Here are the findings, summarized in a slide presentation given by June Kinoshita, FSH Society executive director, at the European Neuromuscular Center’s international workshop on FSHD patient registries. Download here: FSHSociety-ENMC Workshop
Team FSHD Cycling, formed by George Pollock Jr., will participate in the Open Division as an 8 person team in this year’s Race Across America, one of the most respected and longest running ultra-endurance events in the world. Racers must cycle 3,000 miles across 12 states and climb over 170,000 vertical feet. The 2017 RAAM begins in Oceanside, California, on June 13, and ends approximately 10 days later in Annapolis, Maryland. Team FSHD Cycling is racing to raise awareness of FSH Muscular Dystrophy and has a goal to raise $101,000 for the FSH Society. Visit the Team FSHD Cycling web page for details about the route and team.
Support Team FSHD Cycling through a gift! Continue reading