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
Johns Hopkins and the Kennedy Krieger Institute are currently recruiting for two studies! Volunteering for studies like this helps provide researchers with the information they need to provide better treatments, understand the mechanisms of the disease, and search for a cure.
For Family Members (no travel necessary!):
The Johns Hopkins Hospital and the Kennedy Krieger Institute are looking for first-degree relatives of FSHD patients ages 35 and older who do not currently show symptoms. Volunteers will be asked to give a blood draw, which can be performed at any local lab. The blood draw, the genetic test, and shipping will be covered by the study.
Interested individuals should contact Pegah Dehghan: email@example.com.
Study Protocol Number: NA-00019985.
For Patients: Continue reading
In 2014, a Dutch team reported that aerobic exercise training (AET) and cognitive behavioral therapy (CBT) decreased fatigue and improved the quality of life significantly in FSHD patients. Now, the same group has published a study demonstrating that not only did patients given AET or CBT feel more energized and active, but that their muscles degenerated more slowly than in patients who received standard care.
Strikingly, the effect was largest in the CBT group. CBT often focuses on how your thoughts can influence your behaviors and the choices you make. It is often used to treat patients with chronic illness to improve their functioning in their daily life. Continue reading
Newly Formed Facioscapulohumeral Muscular Dystrophy Consortium Aims to Consolidate More than 13 Patient Registries in Effort to Accelerate Research on Rare Disease
BOSTON – (February 22, 2017) – Today the FSH Society, a world leader in combating facioscapulohumeral muscular dystrophy (FSHD), announced that with the FSHD Champions, an international alliance of FSHD patient advocacy organizations, a consensus has been reached to move forward with the vision of an international global FSHD patient registry. The goals of the registry will be to accelerate research to understand and treat FSHD, and empower patients to gain insights from the data about their condition and improve their health and quality of life. 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.
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
Cell Lines to be made available through the NIGMS Human Genetic Cell Repository, sponsored by the National Institute of General Medical Sciences at Coriell Institute for Medical Research
(From PRWeb) The FSH Society, the Massachusetts-based non-profit and global leader in the quest to understand and treat facioscapulohumeral muscular dystrophy (FSHD), today announced the publication of an important collection of cell lines from individuals with FSHD that will soon be available through the NIGMS Human Genetic Cell Repository at Coriell Institute for Medical Research. Comprised of cell lines from 114 patients representing 12 multigenerational FSHD families, this collection is an invaluable new resource for scientists seeking to understand and develop treatments for one of the most common forms of muscular dystrophy. Continue reading
Participants at the ENMC workshop of FSHD registries
International workshop in November reaches consensus on a global FSHD patient registry.
If you are an individual with FSHD, or a family member, you may have been asked to join a patient registry. Perhaps you are wondering what a registry is?
Disease registries are an essential tool for advancing research to understand a disease, improve patient care, and develop treatments. Typically, registries collect patient contact information, and demographic and diagnosis data. In addition, registries may collect varying amounts of data about your health and symptoms. The data will be anonymized and accessible only by authorized individuals, to protect the privacy of patients and families who participate. Continue reading