AREAS OF RESEARCH
Finding treatments and a cure for FSHD is going to need research from all areas from basic science to clinical trials. FSHD Global Research Foundation is committed to funding all types of research to help drive discoveries that may lead to effective treatments for people with FSHD.
Basic research covers the scientific discovery side of research. From understanding what the genes involved in FSHD are doing, to how they interact with the environment to lead to progressive muscle weakness Diagnostics are the tools used to tell if someone has a certain condition. This could be a blood test, an imaging test or a genetic test.Read more +
Diagnostics are the tools used to tell if someone has a certain condition. This could be a blood test, an imaging test or a genetic test. Diagnostics are usually built around a particular aspect of a condition that most people have. For example, in diabetes, most people have high blood sugar. Tests in diabetes focus on measuring blood sugar levels and comparing it to levels you would see in people without diabetes.
For FSHD, genetic tests are used to look for common genetic mutations, but diagnosis can also include tests on muscle function. FSHD Global is exploring ways to improve diagnostics for FSHD in Australia to help ensure people who suspect they have the condition have timely access to a definitive diagnosis.
Therapeutic is the area of creating treatments for conditions. These can be medicines or physical therapies to help improve quality of life. Research in this area may also include trying to get a better understanding of what people with FSHD go through in their lives to help develop treatments that alleviate these things. For example, FSHD Global is funding a study into bone health in people with FSHD. Results from this trial will help clinicians develop better treatment programs that help support optimal bone health. This could be different types of physical therapy, particularly at early stages of the condition, or by making medicines that support bone health available to people with FSHD.
Title: Investigation into the role of FHL1, Calcineurin and NFAT in reducing muscle wasting in FSHD
Title: Derivation of human embryonic stem cells to aid medical research in FSHD
Title: Biomarkers in FSHD, a metabolome study in blood, urine and muscle
Title: Comparing the DnaselHypersensitive Chromatin Landscape at 4q35 of FSHD and Control Cells
Title: Defining the mechanism controlling musclespecific gene expression in FSHD
Title: Deciphering the longdistance interactions of the D4Z4 array in control and FSHD cells
Title: Molecular Genetic Basis of Facio Scapulo Humeral Dystrophy
Title: Dysregulated Pathways in FSHD: Recreating the FSHD Phenotype
Title: Investigation of the role of FHL1 as a novel therapeutic target to reduce muscle wasting and promote muscle regeneration in the frg1 mouse model of FSHD
Title: Study of DUX4 and DUX4c gene expression in human embryonic stem cells
Title: The development of an antiDUX4 therapeutic based on chemical inhibitors of DUX4
Title: Culture and Expansion of DUX4 in Human Embryonic Stem Cells Carrying FSHD
Title: Bill Moss AO Fellowship for Dr Leslie Caron
Title: Tissue-specific silencing of the Planar cell polarity gene FAT1 as a causal mechanism for FSHD
Title: Study on the clinical features, expression profiling, and quality of life of infantile onset FSHD
Title: FSHD drug discovery based on chemical inhibitors of DUX4
Title: Identification of drugs for the normalization of aberrant FSHD candidate gene expression
Title: Drugtargeting of myoblast fusion as a treatment for FSHD
Title: Enhancing BMP signaling to treat FSHD
Title: Application of novel isoflavones in an FSHD hESC model system
Title: HDL based therapy is a potential treatment for FSHD
Title: AO Transporter
Title: A multicenter natural history and biomarkers study of infantile onset FSHD
Title: DUX4 inhibition as a therapeutic strategy for FSHD
Title: Recreating the human chromosomal genetic defect responsible for FSHD in a mouse model.
Title: Evaluation of antisense strategies to suppress DUX4 expression in FSHD
Title: Increasing SMCHD1 Levels as a Therapy for FSHD1 & FSHD2
Title: Clinical Study of Bone Health in FSHD
Title: Generation of Drosophila-Based Biomedical Models of FSHD
Title: Functional study of a novel candidate gene for FSH (LRIF)
Title: Preclinical Studies of Fisetin and VBP15 in Facioscapulohumeral Muscular Dystrophy
Title: Targeting DUX4 using gene-silencing oligonucleotides in FSHD models
Title: Effect of creatine monophosphate on strength and muscle mass in children with FSHD
Title: Small molecule inhibitors of DUX4 as FSHD therapeutics
Title: High throughput chemical screens for activators of SMCHD1, as potential therapeutics for FSHD
MEET THE SCIENTISTS
Associate Professor Jean Mah
Grant assigned: Grant 18 – A multicenter…
The FSHD Global Research Foundation’s mission is to improve the lives of people with FSHD through the advancement of research and development of new treatments. We are therefore committed to funding quality research from around the world
Our research is entirely funded through charitable donations and we fund basic, clinical and therapeutic research. We are interested in hearing from any clinician or scientist who is currently working on FSHD, or has an interest in moving into FSHD research. .
We have several rounds of applications each year. As funding rounds open information will be posted here about the grants that are available and the application process.
TAKE PART IN CLINICAL TRIALS
A clinical trial is a type of study that uses humans as the subject. Clinical trials can be studies that are trying to understand a disease process in humans, such as the recent study into bone health in people with FSHD funded by the Foundation.
Clinical trials humans to test a particular treatment or medical test. For a medicine or medical test to be considered OK for people a rigorous series of trials needs to be performed. These trials need to show that the medicine or medical test works – does it make the symptoms go away or improve? The trial needs to show that the medicine or medical test is safe – does it make any other symptoms appear or become worse?
These trials obviously need people to volunteer to be part of them. This is not a decision to make lightly. While every effort is made to ensure people who are involved in trials are exposed to as little risk as possible, the very nature of a trial means that there are still risks. Clinical trials involve new medicines or medical tests and sometimes the effect in people can be unpredictable.
How can I take part in a clinical trial?
FSHD Global will periodically post information on here about clinical trials that may be looking for participants in Australia.
Before you make any decision to be part of a clinical trial it is important to discuss this with a health professional you trust.
For more information about clinical trials see Australian Clinical Trials website.
The process of developing treatments and a cure is usually a long and convoluted. The power of the biotech industry is to fast-track research progressing ideas into the clinic and ultimately to treatments in a fraction of the time traditional medical research takes.
Globally there are now several biotech companies working in the area of FSHD. This is a game changer for this disease. Biotech can expedite the research process turning the good ideas generated by researchers working on FSHD into effective treatments.
The main difference between traditional medical research and biotech is the ability to approach the challenges of developing treatments for FSHD through the lens of a business model. These two approaches are complementary, this synergy helps to fast-track our goal of overcoming FSHD together.
The Foundation is excited about being part of this research revolution. If you would like to learn more about which biotech companies around the world are working on FSHD, please contact the Foundation.
THE HISTORY OF FSHD
FSHD first described by French physicians Louis Landouzy and Joseph Dejerine.
The same physicians publish a paper on FSHD which describes the familial pattern of the condition.
It was not until 1952 that a formal definition of the clinical features of FSHD was developed. This was based on a large family (1249 individuals!) from Utah who were affected by FSHD. The study was the first to describe the inheritance and the term FSHD was coined.
FSHD is linked to alterations on the long arm of chromosome 4 near the tip (4q35)
FSHD is linked to recombination event that shortens a region in the 4q35 area
The region associated with FSHD is found to have multiple repeat units (D4Z4) with FSHD being associated with fewer than 11 D4Z4 units.
Sequencing of the region associated with FSHD shows that it does contain a gene, but that the D4Z4 region does not.
FSHD Region Gene 1 (FRG1) is discovered beside the D4Z4
Identical twins are discovered who have the exact same genetic mutation, but very different symptoms.
The DUX4 gene discovered
The link between reduced D4Z4 regions and increased amounts of protein from genes in that area is first described.
DUX4 is shown to be toxic to muscle cells and increased amounts of DUX4 are seen in muscle cells from people with FSHD
FSHD Global Research Foundation established
Prevalence* of FSHD estimated to be 4 per 100,000 by Orpha.net. Now estimated at 1 in 7,500
One of the most important parts of science is telling people about your results. This is usually done in the form of a paper in a scientific journal. Results from all experiments should be written up and published. This way scientists, clinicians and the community can see what works, what doesn’t and it gives the researcher who did the work ownership of the project.
FSHD Global encourages researchers we fund to publish as much of their work as possible to help drive the discovery of treatments and cures.
Here are a number of articles written about studies that were possible through FSHD Global funding. Many of these will also have summaries written about them in the blog section of the website.
Read previous publications
- Davide Gabellini 2016
- Consensus Paper 2016
- Silvere van der Maarel 2016b
- Silvere van der Maarel 2016
- Marnie Blewitt 2015
- Silvere van der Maarel 2015c
- Silvere van der Maarel 2015b
- Silvere van der Maarel 2015
- Scott Harper 2015
- Alexandra Belayew 2015
- Silvere Van der Maarel 2015
- Christine Mitchell 2015
- Francoise Helmbacher 2015
- Davide Gabellini 2014c
- Davide Gabellini 2014b
- Davide Gabellini 2014
- Michael Kyba 2014
- Francoise Helmbacher 2013
- Yi-Wen Chen 2013
- Davide Gabellini 2013c
- Davide Gabellini 2013b
- Davide Gabellini 2013
- Melanie Ehrlich 2012
- Alexandra Belayew 2012
- Davide Gabellini 2012c
- Davide Gabellini 2012b
- Davide Gabellini 2012
- Scott Harper 2012
- Davide Gabellini 2011
- Melanie Ehrlich 2011
- Frederique Magdinier 2010
- Christine Mitchell 2008
4q35. A term that defines where on the chromosomes the chromosomal deletion associated with FSHD Type 1 is. It may be useful to think of it as an address. In this case, the deletion is on chromosome 4, on the “q” (long) arm at region 35.
4q35 genes. A group of genes that are located in the 4q35 region (Chromosome 4, long arm, region 35). Some of these genes will have their activity controlled by the D4Z4 repeat array.
Allele. Humans have two sets of chromosomes, and therefore two copies of each gene. One copy is inherited from your mother, the other from your father. These two copies are called alleles.
Antibody. Proteins produced by the immune system, which bind very specifically to unique features of other proteins and molecules. The immune system uses antibodies ability to bind to specific proteins to destroy foreign materials.
Antisense†oligomers. Single stranded chains of genetic material that bind to specific RNA preventing them making protein. Oligomers are used to stop the production of a particular protein.
Autophagy. This is how cells tidy up their components. By degrading unnecessary or dysfunctional components. This is done via the lysosome which act a little like a household garbage disposal unit.
Binding. The interaction of one molecule with another. This can describe a molecule sticking to another (eg. an antibody ‘binding’ to its target protein), or attaching to a cellular component to change its activity (eg. A protein that opens up a channel on the surface of the cell).
Biomarker. Measurements that may indicate a persons health status, such as tests of muscle strength, a blood test or imaging. A diagnostic biomarker will show if a person is likely to have a disease. Therapeutic biomarkers show if a therapy is likely having the desired effect.
Chromatin. The combination of DNA and proteins (primarily histones) that make up the contents of the nucleus of a cell. The main functions of chromatin are to package DNA into a smaller volume, to strengthen the DNA to allow cell division, to prevent DNA damage, and to control gene expression and DNA replication.
Chromosome. Found inside the cell nucleus, a recognizable structure comprising genes, regulatory elements and other nucleotide sequences. In humans, each cell nucleus contains 23 distinct pairs of chromosomes.
Clinical trial. Tests of drugs, diagnostics and other health interventions in human volunteers conducted to see whether the interventions being tested are safe and effective.
Cytoplasm. The cytoplasm is the jellylike part of the cell lying between the cell membrane and the nuclear membrane.
D4Z4. A repeated DNA segment of approximately 3,200 nucleotide bases. Loss of these repeats at chromosome locus 4q35 is associated with FSHD Type 1. The number of repeats can vary significantly in different individuals and can be used to diagnose FSHD and predict severity of the condition. Each D4Z4 contains a DUX4 gene. (D4Z4 gets its name from: D for DNA segment (of unknown or ‘anonymous’ nature); 4 for chromosome 4; Z to distinguish it from S (which represents a single sequence occurrence) and represents a repetitivetype sequence entity; 4 representing the fourth member of this ‘class’ of sequences identified on chromosome 4.)
Deletion. Loss of part of a DNA molecule, as in “deletion of D4Z4 repeats at 4q35” associated with FSHD.
Differentiation. The process by which a less specialized cell (e.g. in an embryo) becomes a more specialized cell type, such as skin, heart, muscle, or neuron. In adults, there are many types of stem cells that differentiate into more specialised cells such as during wound healing, creating new blood cells and creating sperm.
DNA. The molecule that defines our genetic inheritance. It contains all the instructions for constructing and operating a living organism. DNA is made of four simple units, or “nucleotide bases”, whose specific sequence “spells out” genetic information.
DUX4.(Double homeobox, 4). A copy of the DUX4 gene is located within each D4Z4 repeat array on chromosome 4. Inappropriate expression of DUX4 in muscle cells is thought to contribute to FSHD.
Epigenetics. Refers to modifications that change gene function but do not change the underlying DNA sequence. Examples of these modifications are DNA methylation and histone modification, both of which serve to regulate how a gene becomes expressed as protein. Some of these changes have been shown to be heritable.
Expression profiling. The first step in converting genetic information to an observable trait involves the transfer of information from gene to protein through an intermediate molecule called RNA. Measuring all of the RNA produced in one definable moment creates a global picture of how a cell is functioning and produces a profile of total expression activity.
FISH. (fluorescentin situhybridization). A laboratory technique, commonly used when assessing genetic conditions. The technique uses fluorescent molecules to detect particular DNA sequences on chromosomes. The fluorescent molecules let you see where the DNA sequence is on the chromosome.
Gene. Genes specify the instructions needed to produce an observable trait such as eye colour, hair colour, or more complex traits like FSHD. A gene is a basic hereditary unit and is defined by specific segment of DNA.
Gene expression. The initial step in converting the information contained in a gene, as DNA, to an observable character through an intermediate molecule RNA.
Gene locus. Physical location, or address, of a gene on a chromosome.
Genotype. The actual DNA sequence a cell, an organism, or an individual, usually with reference to a specific characteristic under consideration.
Germ line. The collection of biological cells that give rise to gametes (that is, the egg or sperm).
Homeobox. A DNA sequence found within genes that are involved in the regulation of patterns of anatomical development. For example, homeobox genes are involved with development of the embryo and ensure the cells and structures are formed according to the DNA instructions.
Histones. The chief protein components of chromatin, acting as spools around which DNA winds. Histones play a role in gene expression.
Immortalized cells. Cells that continue to divide indefinitely, unlike normal cells which with normal aging cease to divide.
Immunocompromised. A state in which the immune system is defective and unable to mount an immune response against disease pathogens or other foreign cells.
Innervate. Formation of a functional connection between nerve and muscle or other target tissue.
Longitudinal study. A research study involving repeated observations of the same variables in the same individuals over long periods of time.
Lysosome. Cellular organelle that contain enzymes that break down waste materials and cellular debris.
Magnetic resonance imaging (MRI). A medical imaging technique using the property of nuclear magnetic resonance to image nuclei of atoms inside the body. MRI can create more detailed images of the human body than are possible with Xrays.
Magnetic resonance spectroscopy (MRS). A research technique using nuclear magnetic resonance to provide information about chemical properties of atoms and molecules.
Methylation. In biological systems, the addition of a methyl group to DNA, which can regulate the expression of genes. Some methylation changes are heritable.
Molecular pathway. A chain of chemical reactions occurring within a cell.
Mutation. A change in the nucleotide sequence in the genome of an organism with perceived deleterious effects.
Myocyte. Long, tubular cells found in muscle. Myocytes develop from myoblasts to form skeletal muscle fibers (myotubes) in a process known as myogenesis.
Nucleus. The cell nucleus contains all the genetic material (DNA) for the cell enclosed by a membrane.
Organelle. A specialized unit within a cell that has a specific function, for example, the nucleus contains all the genetic material and organelles called mitochrondria provide the cell with energy.
Pathophysiology. Physiological processes or mechanisms that lead to the development and progression of diseases and conditions.
Phenotype. The composite of an organism’s observable characteristics or traits, such as its physical form, growth, biochemical and physiological properties, and behavior.
Pluripotent cells. A stem cell that has the potential to differentiate into diverse types of cells. Induced pluripotent stem cells (iPS cells or iPSCs) are a type of pluripotent stem cell that has been made from a normal adult cell. It is turned back into a stem cell by forcing it to express certain genes.
Polycomb. A family of proteins that can alter chromatin such that genes are epigenetically silenced (not able to be expressed).
Protein. Biological molecule consisting of chains of amino acids. Proteins are the principal products of genetic information and they do the bulk of work required for life. They perform a vast array of functions within living organisms, including providing cells with structure, transmitting signals, and transporting molecules from one location to another.
Protein synthesis. The production of proteins within cells by using information encoded in genes. The genetic code on DNA is transcribed into messenger RNA, and then translated into a chain of amino acids to form protein.
Reprogramming. Conversion of a cell from one cell type to another. This involves a conversion first to a pluripotent state, then redifferentiating to the new cell type.
RNA (Ribonucleic acid). A family of large biological molecules that perform vital roles in the coding, decoding, regulation, and expression of genes. Like DNA, RNA is assembled as a chain of nucleotide “bases”, but, unlike DNA, it is usually singlestranded.
Somatic cell. The term somatic cell describes any cell forming part of the body. This excludes the reproductive cells or ‘germ line’ cells, or stem cells.
Stem cell. Undifferentiated cells that can differentiate into a variety specialised somatic cells and can divide to produce more stem cells.
Target. A protein or nucleic acid (DNA or RNA) whose activity can be modified by an external stimulus, such as a drug or another biological molecule (e.g. hormone, antibody, neurotransmitter, etc.). For example, one ‘target’ for FSHD research is the DUX4 protein.
Telomere. A region of repetitive nucleotide sequences at the tip of the arm of a chromosome, which protects the end of the chromosome.
Transcription. The copying of DNA into messenger RNA during the process of gene expression.
Transgenic. An organism that has had genetic material (or transgene) introduced into its genome that is not its own so that it will exhibit a new property.
Translation. The process of ‘translating’ messenger RNA sequence into protein