A chemical substance which helps to transmit a signal from the nerve to the muscle causing it to contract.
Animals (usually mice or rats) with conditions similar to those affecting humans which can be used to study disease processes and test potential therapies. The animals have a similar gene mutation as that present in the human condition. The mutation is either naturally occurring in the animals or they are specifically bred in the laboratory to have the mutation.
The ‘building blocks’ of proteins. The sequence of amino acids determines the shape, properties and role of the protein.
The removal of a sample of amniotic fluid (the fluid around an unborn baby) for prenatal testing. The fluid is tested for birth defects and genetic problems in the developing baby.
Proteins made by the body to protect itself from “foreign” substances such as bacteria or viruses. They are Y-shaped proteins that specifically recognize and bind to a particular protein sequence known as an ‘antigen’.
The body’s own tissues or DNA. Stem cell therapies are often described as autologous, which means the person’s own stem cells are used for the transplant, rather than a donor’s cells.
All the chromosomes other than the X and Y chromosomes. Humans have 23 pairs of chromosomes, 22 pairs are known as autosomes and one pair is the sex determining chromosomes – X and Y. Autosomal inheritance means that an abnormal gene can affect either sex.
Conditions in which the immune system produces antibodies that attack the body’s own cells, for example, dermatomyositis, polymyositis and myasthenia gravis.
Removal of a small amount of tissue for examination.
BPAP ventilation (or BiPAP)
Bilevel positive airway pressure. A type of non-invasive ventilation that helps with breathing by providing a flow of air delivered through a face mask. The air is pressurized by a machine, which delivers it to the face mask through long, plastic tubing. The machine delivers the air at two different pressures which alternate: A higher pressure to breathe in (called inspiratory positive airway pressure, or IPAP) and a lower pressure for breathing out (called expiratory positive airway pressure or EPAP).
To do with the heart.
An individual who has inherited a genetic mutation but does not have any symptoms. They have one normal and one abnormal copy of a pair of genes which cause a genetic disorder. A carrier will usually remain unaffected throughout his or her life but may pass the faulty gene on to their children.
Tests to find out if a person who does not show symptoms of a condition nevertheless carries the gene and could pass it on to his or her children.
The basic structural unit of all living organisms. They are often called the building bricks of life. The cell is surrounded by a membrane. Inside the cell is a structure called the nucleus. The nucleus contains DNA arranged into chromosomes. Humans have an estimated 100 trillion cells.
A technology that relies on replacing diseased or dysfunctional cells with healthy, functioning ones. These cells could be from a donor or the patient’s own cells that have been modified in some way. Stem cells are an important type of cells used for cell therapy.
Chorionic Villus Sampling (also known as CVS)
Removal of chorionic villa for prenatal testing. The chorionic villa are cells situated on the wall of the uterus (womb) which form the early placenta (afterbirth). They have the same genetic make-up as the unborn baby and can be tested to detect certain abnormalities.
Sausage shaped bundles of DNA in the cell nucleus (the control centre of a cell). They are made of a very long thin strand of DNA coiled upon itself many times. Humans have 46 chromosomes (23 pairs) in most cells of their bodies. The only exception is the unfertilized egg and sperm cells which contain only 23 unpaired chromosomes each. Fertilization of a 23-chromosome egg by a 23-chromosome sperm produces a new 46-chromosome cell which grows into a new individual. In this way one half of each chromosome pair is inherited from each parent.
Present at birth or soon afterwards.
Shortening of muscles or tendons which prevents the associated joints from moving freely.
Creatine Kinase (CK or CPK)
An enzyme normally present in muscle which is released into the blood when muscle is damaged. Therefore, elevated levels in blood indicate muscle (including heart muscle) has been damaged by injury or disease. Some forms of muscular dystrophy are associated with high levels of creatine kinase in a blood test.
The loss of a piece of genetic material from a chromosome or gene.
A sheet of muscle that extends across the bottom of the rib cage which is crucial for breathing.
Away from the centre of the body, for example, the hands and feet.
DNA (Deoxyribonucleic Acid)
The molecule that contains the genetic instructions for the functioning of all known living organisms. DNA is often compared to a set of blueprints or a recipe, or a code, since it contains the instructions needed to construct other components of cells, such as proteins. DNA is divided into segments called genes. Each cell’s chromosomes contain about two metres of DNA yet it is so thin that it is barely visible even with the most powerful microscope. If all of the DNA in a human body were stretched end to end it would be long enough to reach the moon and back about 10,000 times.
A method of genetic inheritance, whereby a single abnormal copy of a gene causes disease, even though a good copy of the gene is also present. We inherit one copy of each gene from our mother and one from our father. Individuals with a dominant condition have a 50% chance of passing on the altered gene, and resulting disease, to their children.
Difficulty in swallowing.
The protein missing in people who have Duchenne muscular dystrophy and reduced in those who have Becker muscular dystrophy. The dystrophin protein normally sits in the membrane that surrounds muscle fibres like a skin, and protects the membrane from damage during muscle contraction. Without dystrophin the muscle fibre membranes become damaged and eventually the muscle fibres die.
Relating to, or afflicted with dystrophy. Muscles affected by muscular dystrophy may be described as dystrophic.
A disorder in which an organ or tissue of the body wastes away. Muscular dystrophy refers to a group of disorders in which the muscle gradually gets weaker and wastes away.
Where a part of a chromosome or gene is repeated.
The use of ultrasound to produce images of the heart.
A test which records the electrical activity of the heart through electrodes attached to the skin.
A test that assesses the electrical activity of the muscles and the nerves controlling the muscles. It is used to help diagnose neuromuscular disorders. There are two kinds of EMG in widespread use: intramuscular (needle) and surface EMG. To perform intramuscular EMG, a needle electrode or a needle containing two fine-wire electrodes is inserted through the skin into the muscle tissue. Intramuscular EMG may be considered too invasive or unnecessary in some cases and an electrode placed on the surface of the skin is used.
A protein which initiates, facilitates or speeds up a reaction. Almost all of the processes that occur in our body require enzymes. The enzymes in the stomach, for instance, ensure that food is cut into tiny particles that can be converted into energy in the body.
Genes are divided into regions called exons and introns. Exons are the sections of DNA that code for the protein and they are interspersed with introns which are also sometimes called ‘junk DNA’.
A therapeutic approach currently in clinical trial for Duchenne muscular dystrophy. It involves small pieces of DNA called “molecular patches” or “oligonucleotides” which mask a portion of a gene where there is a mistake, or mutation. The name comes from “exon” which are the segments that genes are divided into. For example, the dystrophin gene (which is affected in Duchenne muscular dystrophy) is divided into 79 exons. It is called “skipping” because the molecular patch causes the body to ignore or skip-over an exon.
Insertion or deletion of a number of “letters” of DNA code not divisible by three. The DNA code is read three “letters” at a time so such mutations disrupt the reading of the gene.
A tube inserted through the abdomen that delivers nutrition directly to the stomach. It’s one of the ways doctors can make sure people with trouble eating get the fluid and calories they need.
Genes are made of DNA and each carries instructions for the production of a specific protein. Genes usually come in pairs, one inherited from each parent. They are passed on from one generation to the next, and are the basic units of inheritance. Any alterations in genes (mutations) can cause inherited disorders.
The process by which people at risk of an inherited disorder, are advised of the probability of developing the condition themselves or passing it on to their children. Information is also provided on the consequences and nature of the disorder and the options open to them in management and family planning.
Conditions which result from alterations in the genetic make-up of an individual. They may be the consequence of defects in single genes or in whole chromosomes: parts of which may be lost, duplicated or misplaced.
A DNA sequence with a known physical location on a chromosome. Genetic markers can help link an inherited disease with the responsible gene. DNA segments close to each other on a chromosome tend to be inherited together. Genetic markers are used to track the inheritance of a nearby gene that has not yet been identified, but whose approximate location is known. The genetic marker itself may be a part of a gene or may have no known function.
Treatment of a disease by introducing a new gene into a cell. The new gene may be used to replace a function that is missing because of a defective gene. Viruses are often used to deliver the new gene into the cells.
The complete set of genes in a person or organism.
Term referring to one’s genetic make-up.
A protein with a carbohydrate (sugar) molecule attached.
The body’s response to ‘foreign’ material, such as bacteria, a virus or transplanted cells or tissue.
The body’s reaction to injury or infection. Inflammation results in redness, pain, swelling, and warmth, due to increased blood flow in the traumatized area. It is a protective attempt by the body to remove whatever is causing the injury or infection (for example a splinter in your finger or a virus in your lungs) as well as initiate the healing process.
In vitro fertilisation (IVF)
A process by which eggs are fertilised by sperm outside the womb. The fertilised egg is then transferred to the patient’s womb to try to establish a successful pregnancy.
Studies that look for patterns of inheritance of genetic markers in large families in which a particular condition is common. The aim is to identify a genetic marker that is always inherited by those family members with the disease but not by those who do not have the disease. This information can then be used to narrow down the region of DNA until the causative gene is identified
A female carrier of an X-linked condition (such as Duchenne muscular dystrophy) who exhibits symptoms such as muscle weakness.
A mouse model of Duchenne muscular dystrophy. These mice have a genetic change in the dystrophin gene – the gene that is also altered in boys with Duchenne. The muscles of these mice have many features in common with the muscles of boys with Duchenne muscular dystrophy.
The energy factories of cells. They have their own DNA, inherited from the mother. Mutations in the mitochondrial DNA can cause neuromuscular conditions called mitochondrial myopathies.
See ‘animal model’
The basic unit of muscle tissue formed by the fusion of groups of long, cylindrical muscle cells.
A change to the DNA code. Parts of the DNA code may be deleted, duplicated or replaced with different code. Depending on where this change occurs and the type of change, they can either have no effect or result in genetic diseases such as muscular dystrophy. Mutations can be passed down through the generations of a family.
A cell that is a precursor to muscle fibres.
Myoblast transfer therapy
A potential method of treatment for muscular dystrophy which involves the transplantation of billions of healthy donor cells into muscle. This is sometimes known as cell therapy.
A condition affecting muscle, usually without involvement of the nerves.
The cord-like bundles of fibres or “wires” which transmit signals around the body. Nerves form a network of pathways for conducting information throughout the body. For example, the brain sends a signal down the nerves to tell a muscle to contract.
Where a muscle fibre and a nerve meet.
A nerve cell that receives and conducts electrical impulses from the brain.
A medical term to describe disorders of the nerves which carry signals to and from the muscles in the legs and arms. These nerves are known as the peripheral nerves. Charcot-Marie-Tooth disease is one example of a neuropathy.
Next generation sequencing
A cutting edge technology that allows researchers to ‘read’ the whole of an individual’s genome. Researchers have recently started to use it for finding new genes and diagnosing genetic conditions more accurately.
A change in the DNA which causes a premature stop signal to occur in a gene. When this happens the protein is not produced.
Nucleus (plural nuclei)
Structure in the centre of each cell which contains the chromosomes with their genetic material.
Devices or aids such as braces or special footwear to support and aid the movement of the limbs or spine and prevent or correct deformities.
Short chains of amino acids. The chains are usually less than 50 amino acids long. Peptides are smaller than proteins, which are also chains of amino acids. By comparison the largest known human protein is around 30,000 amino acids long.
Phase 0 clinical trial
A trial conducted very early in a small number of patients (perhaps less than 10). The purpose of phase 0 trials is to discover the therapeutic potential of a drug and to evaluate whether the drug development is worth continuing further. Unlike the phase I clinical trials, phase 0 trials are not used to evaluate in detail the drug dosage, treatment safety or side effects.
Phase 1 clinical trial
The first stage of testing a drug or treatment in human subjects. Researchers test a new drug or treatment in a small group of people – often healthy volunteers rather than patients. This phase is to evaluate the treatment’s safety, determine a safe dosage range, and identify side effects. About 70 percent of experimental drugs pass the initial phase of testing.
Phase 2 clinical trial
Are designed to test how well the drug or treatment works as well as to continue safety assessments on a larger group of patients (20-300). When the development process for a new drug fails, this usually occurs during Phase 2 trials when the drug is discovered not to work as planned, or to have toxic effects. Only one-third of experimental drugs successfully complete both phase 1 and phase 2 studies. Sometimes written as Phase II trial.
Phase 2a and Phase 2b clinical trial
Phase 2 studies are sometimes divided into Phase 2a and Phase 2b. Phase 2a is specifically designed to assess dosing requirements (how much drug should be given), whereas Phase 2b is specifically designed to study efficacy (how well the drug works at the prescribed dose(s)). Sometimes written as Phase IIa and Phase IIb.
Phase 3 clinical trial
Test a new drug on a larger number of patients after they have been shown to be effective in a phase 2 trial. Phase 3 trials often enroll large numbers of people and may be conducted at many centres nationally or internationally. These phase 3 studies allow researchers to determine the tolerance and the effectiveness of the product and therefore to assess the benefit/risk ratio of the drug. Seventy to 90% of drugs entering phase III will be candidates for a marketing approval application. Sometimes written as Phase III trial.
Phase 4 clinical trial
Evaluates the long term risks and benefits of a drug or treatment once it’s available on the market. They are designed to detect any rare or long-term effects in a much larger patient population and over a longer time period than was possible during the Phase 1 to 3 clinical trials.
The outward appearance and observable characteristics of an individual. It is the product of interactions between genes and the environment.
An inactive substance designed to resemble the drug being tested. It is used to rule out any benefits a drug might exhibit because the recipients believe they are taking it.
Placebo-controlled clinical trial
A clinical trial where some of the participants receive a placebo treatment – an inactive substance designed to resemble the drug being tested. Usually these trials are “blinded” so that the participants and the researchers do not know who is receiving the real treatment and who is receiving the placebo. This clinical trial design is used to rule out any benefits a drug might exhibit because the recipients believe they are taking it and to eliminate any bias on the part of the researchers measuring the benefit of the treatment.
Diagnosis of a genetic disorder before there are any symptoms of that disorder.
Pre-implantation genetic diagnosis (PGD)
The testing of very early embryos for a specific genetic condition before they are implanted into the womb. Couples undergo standard in vitro fertilisation (IVF) during which eggs are fertilised by sperm outside the womb. The embryos are grown in the laboratory until they consist of eight cells. A single cell is then removed from the embryo and the DNA is tested for the presence of the mutation gene.
Testing for diseases or conditions in a foetus or embryo before it is born. This is done by analysing the DNA in a sample of the fluid or tissue surrounding the foetus. The sample is collected by procedures called amniocentesis or chorionic villus sampling. See also “non-invasive prenatal diagnosis”.
Predicted course and outcome of a disorder.
Large molecules composed of one or more chains of building blocks called ‘amino acids’ in a specific order. The order is determined by the gene that contains the instructions for the construction of the protein. Proteins are required for the structure, function, and regulation of the body’s cells, tissues, and organs. They are the building blocks of our bodies. We have millions of different proteins in our body and each has unique functions. Two examples are the enzymes in our stomach that digests our food and the collagen which holds our skin together.
Close to the centre of the body.
Randomised controlled trial
A clinical trial where treatments and placebo are allocated randomly to participants rather than by conscious decisions of clinicians or patients.
A form of inheritance in which a faulty copy of a gene is inherited from each parent. In order to develop the disorder an individual has to have two copies of the faulty gene. If a person has inherited one faulty gene and one normal gene he or she will not be affected but will be a gene carrier. If both parents are carriers of the same faulty gene the likelihood of a child inheriting the condition is 25 percent, or 1 in 4.
Ribonucleic acid (RNA)
Ribonucleic acid, a substance very similar to DNA. When a gene is ‘switched on’, RNA carbon copies of the gene’s code are made. The RNA moves outside the nucleus where they direct the manufacture of proteins. DNA can be thought of as a recipe book in the library that you can’t take out. RNA is a photocopy of a recipe that you can take home to cook something in your kitchen (making the protein).
Curvature of the spine.
The X and Y chromosomes determine the sex of an individual. Females have two X chromosomes: males have an X and a Y chromosome. The other 22 pairs of chromosomes are called the ‘autosomes’.
A type of muscle which is striated in appearance and usually attached to tendons. It is used to create movement, by applying force to bones and joints; via contraction. Other types of muscle include cardiac (heart) and smooth (blood vessels, stomach, intestines) muscle.
Cells that have not yet specialised to form a particular cell type, and can still become muscle cells or other types of cell.
Drugs that are similar to some of the hormones produced by the body. They are classed as anabolic (used illegally by athletes to build up muscle) or corticosteroids. Corticosteroids are similar to natural hormones produced by the adrenal glands that reduce inflammation and suppress the immune response. They are often prescribed to boys with Duchenne muscular dystrophy. These steroids may have an effect on stabilising or even improving muscle strength for a period of time but side effects are relatively common. The main steroid that is used is called prednisolone (prednisone in the USA). Deflazacort is also used in some countries. Sometimes also referred to as ‘glucocorticoids’.
This is a technique which uses reflected sound waves to see the internal structures of the body. It is now widely used in medicine for example to obtain images of muscle structure and internal organs or of the unborn child.
A very similar protein to dystrophin. Low levels of utrophin are present in everyone – including individuals with Duchenne muscular dystrophy – but in insufficient amounts to compensate for the loss of dystrophin.
Assistance in breathing by mechanically pumping air/oxygen into the lungs.
Viruses consist of genetic materials (DNA or RNA) surrounded by a protective coat of protein. They are capable of latching onto cells and getting inside them. Viruses are too small to be seen by the naked eye. They can’t multiply on their own, so they have to invade a ‘host’ cell and take over its machinery in order to be able to make more virus particles. They can be made harmless by changing their genetic code.
A form of inheritance where the gene in question lies on the X chromosome. X-linked genes can be dominant but are usually recessive. Girls who carry an altered gene are usually not affected since they have a second normal copy of the gene. They are carriers, however, and can pass the affected gene on in 50% of their pregnancies. Boys who have only one X chromosome do not have a second normal copy of the gene so they will be affected by the disorder in question. Men with an X-linked condition will pass on the altered gene to all of their daughters who will be carriers but to none of their sons.
A tropical freshwater fish belonging to the minnow family. There are many advantages of using zebraﬁsh to study human disease and development: Firstly, zebraﬁsh are small in size, and are easy to keep and breed. They are more similar to humans than you think; many genes are shared between humans and zebraﬁsh, including the genes used to make muscles. The genes of zebraﬁsh can be modified; this means we can create mutations in genes which cause human diseases, such as muscular dystrophy. Importantly, zebrafish embryos are transparent, so we can easily observe their muscles developing. Finally, the embryos can be used to look for drugs which may prevent or slow the progression of a disease.