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

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.

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Diagnostics

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.

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Therapeutic

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.

RESEARCH GRANTS


Basic
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MEET THE SCIENTISTS


Professor Alexandra Belayew

Grant assigned: Grant 10 – Study of DUX4 and…
Grant 12 – Culture and Expansion of DUX4 in…
Grant 17 – Evaluation of antisense strategies to…

Doctor Mark Cowley

FSHD Global grantsGrant 37 – The next wave of Whole Genome Sequencing-based FSHD diagnostics, and clinical measures of progress

Professor Silvere m. Van der Maarel Ph. D

Grant assigned: Grant 22 – Increasing SMCHD1…
Grant 3 – Biomarkers in FSHD, a metabolome…

Professor Rabi Tawil

Grant assigned: Grant 8 – Dysregulated Pathways…
Grant 22 – Increasing SMCHD1 Levels as a…

Professor Rosella Tupler

Grant assigned: Grant 5 – Defining the mechanism controlling…
Grant 26 – Functional study of a novel candidate gene for FSH…

Professor Baziel van Engelen

Grant assigned: Grant 3 – Biomarkers in FSHD, a…

Professor Stephen Tapscott

Grant assigned: Grant 22 – Increasing SMCHD1 Levels as…

Associate Professor Monique Ryan

Grant assigned: Grant 18 – A multicenter collaborative study…

Doctor Paul Gregorevic

Grant assigned: Grant 25 – Enhancing BMP signaling to…

Associate Professor Marnie Blewitt

Grant assigned: Grant 22 – Increasing SMCHD1 Levels as…
Grant 39 – High throughput chemical…

Doctor Scott Q. Harper

Grant assigned: Grant 8 – Dysregulated Pathways…
Grant 15 – DUX4 inhibition as a therapeutic strategy…

Doctor Davide Gabellini

Grant assigned: Grant 7 – Molecular Genetic Basis…
Grant 16 – Re-creating the human chromosomal…
Grant 20 – Identification of drugs for the…

Doctor Kathryn Wagner

Grant 23a/b – Clinical Study on Possible Increased…

Professor Alastair Corbett

Grant assigned: Grant 23a/b – Clinical Study on…

Doctor Yi-Wen Chen

Grant assigned: Grant 18 – A multicenter…
Grant 34 – Targeting DUX4 using gene-silencing…

Doctor Frederique Magdinier

Grant assigned: Grant 6 – Deciphering the long-distance…

Associate Professor Jean Mah

Grant assigned: Grant 18 – A multicenter…

Professor Melanie Ehrlich

Grant assigned: Grant 4 – Comparing the Dnasel…
Grant 8 – Dysregulated Pathways in FSHD…

Doctor Robin Fitzsimons

Grant assigned: Grant 14 – Tissue-specific silencing of the Planar…
Grant 16: Re-creating the human chromosomal genetic defect…

Doctor Tomas Stojanov

Grant assigned: Grant 2 – Derivation of human…

Doctor Meagan McGrath

Grant assigned: Grant 1 Investigation into the role…
Grant 9 Investigation of the role of FHL1 as a novel…
Grant 21 Drug-targeting of myoblast fusion as a…

Professor Christina Mitchell

Grant assigned: Grant 1 Investigation into the role…
Grant 9 Investigation of the role of FHL1 as a novel…
Grant 21 Drug-targeting of myoblast fusion as a…

Doctor Stephen Palmer

Grant assigned: Grant 28 – Application of novel…

Doctor Leslie Caron

Grant assigned: Grant 13 – Bill Moss AM Fellowship…
Grant 28 – Application of novel isofavones in an…

Professor Karen Sermon

Grant assigned: Grant 12 – Culture and Expansion…

Professor John Mattick AO, FAA

Grant assigned: Grant 7 – Molecular Genetic Basis of…

Professor Steve Wilton

Grant assigned: Grant 15 – DUX4 inhibition as a therapeutic…
Grant 17 – Evaluation of antisense strategies to suppress DUX4…

Doctor Michael Kyba

Grant assigned: Grant 11 – The development of an anti­DUX4…
Grant 19 – FSHD drug discovery based on…

Professor Francoise Helmbacher

Grant assigned: Grant 14 – Tissue-specific silencing of the Planar…

GRANT APPLICATIONS


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.

BIOTECH


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


  • 1884

    FSHD first described by French physicians Louis Landouzy and Joseph Dejerine.

  • 1886

    The same physicians publish a paper on FSHD which describes the familial pattern of the condition.

  • 1952

    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.

  • 1991

    FSHD is linked to alterations on the long arm of chromosome 4 near the tip (4q35)

  • 1992

    FSHD is linked to recombination event that shortens a region in the 4q35 area

  • 1993

    The region associated with FSHD is found to have multiple repeat units (D4Z4) with FSHD being associated with fewer than 11 D4Z4 units.

  • 1994

    Sequencing of the region associated with FSHD shows that it does contain a gene, but that the D4Z4 region does not.

  • 1996

    FSHD Region Gene 1 (FRG1) is discovered beside the D4Z4

  • 1998

    Identical twins are discovered who have the exact same genetic mutation, but very different symptoms.

  • 1999

    The DUX4 gene discovered

  • 2003

    The link between reduced D4Z4 regions and increased amounts of protein from genes in that area is first described.

  • 2007

    DUX4 is shown to be toxic to muscle cells and increased amounts of DUX4 are seen in muscle cells from people with FSHD

  • 2007

    FSHD Global Research Foundation established

  • 2008

    Prevalence* of FSHD estimated to be 4 per 100,000 by Orpha.net. Now estimated at 1 in 7,500

Publications


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.

GLOSSARY


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. (​fluorescent​​in situ​​hybridization​). ​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