Myelin Project UK. Multiple Sclerosis, Leukodystrophy Research

Adrenoleukodystrophy (ALD)	A rapidly progressive X-linked genetic disorder marked by the accumulation of saturated very long chain fatty acids (VLCFA) in all tissues and body fluids, with a preference for the brain and the adrenal glands. This build up leads to inflammation of the brain and erosion of the white matter of the central nervous system and the adrenal glands. It affects only boys; while there is a neonatal form, it typically strikes between the ages of 6 and 10. Known treatment: Presymptomatic boys can benefit from Lorenzo's Oil, while there is no current treatment for symptomatic boys - although there is ongoing research. Female carriers have been known to develop some symptoms but not as severe or life threatening. Birth rate of ALD averages around 1:17,000.
Adrenomyeloneuropathy (AMN)	The adult form of ALD, milder and more slowly progressive than the childhood form; it affects the spinal cord and peripheral nervous system.
Arylsulfatase A	The lack of this enzyme results in the toxic accumulation of sulfatide deposits in metachromatic leukodystrophy, leading to demyelination of the CNS.
Astrocytes	Star-shaped non-myelinating glial cells.
Asymptomatic	Having a disease without manifestation of symptoms.
Axons	Filament-shaped processes of neurons that conduct impulses away from the cell body. Together with myelin, they are the main constituents of our nerves
Bone marrow	A soft tissue occurring in certain large bones that is responsible for manufacturing most of the body's blood cells.
Canavan disease	A neurodegenerative disease of infancy in which the lack of the enzyme aspartoacyclase results in the build up of N-acetyl aspartate, leading to demyelination in the CNS, as well as increased brain volume and weight and spongy degeneration in the subcortical white matter.
Central Nervous System (CNS)	It comprises the brain and spinal cord.
Demyelination/ dysmyelination	"Demyelination" The destruction, loss or removal of the protective myelin sheath coating the axons, resulting in their inability to transmit impulses. Usually caused by diseases such as multiple sclerosis or the leukodystrophies. "Dysmyelination" refers to a failure of myelin formation.
Embryonic Stem Cell	Totipotent stem cells cultured from early embryo. Embryonic stem cells (ES) are capable of differentiating into several different final differentiated types, such as liver, lung, or neural cells
Enzyme	A protein molecule produced by living organisms to catalyse, or facilitate, a specific chemical reaction involving other substances without itself being destroyed or changed in any way.
Erucic acid	One of the active components of Lorenzo's Oil, it is a 22-carbon monounsaturated fatty acid present in the seeds of the nasturtium flower and of several Cruciferae species (rape, mustard, and wallflower).
Estrogen	A steroidal hormone produced in both males and females that has a variety of functions. In women, it is released during menstruation to form a hospitable environment for embryo fertilisation and implantation in the womb.
Experimental allergic encephalomyelitis (EAE)	A disease induced in laboratory animals that produces symptoms similar to human multiple sclerosis.
Gene	The basic unit of inheritance on a chromosome. Genes encode for proteins that in turn determine the structure and function of all components of the body.
Gene therapy	A novel approach to treat, cure, or ultimately prevent disease by changing or repairing defective genes.
Glia/glial cells	There are two main types of glial cells in the CNS: Oligodendrocytes, which produce, maintain and repair the myelin sheath of the axons, and astrocytes, named for their characteristic star-like shape. Astrocytes provide both mechanical and metabolic support to neurons, regulating the environment in which they function. Other types of glia exist outside the CNS, including Schwann cells.
Gray matter	Otherwise known as the cerebral cortex, or the "thinking matter" of the brain, it is composed of nerve cells and blood vessels.
Growth factors	Substances produced by the body to control growth, division and maturation of cells and tissues.
Immortal Cell Line	Cells, maintained in culture, that are capable of continuously renewing themselves.
Interferons	A group of naturally occurring proteins that act as chemical messengers between cells. Three have so far been discovered, alpha, beta and gamma, all of which have immune-modulating effects. Interferons are used in the treatment of cancer and autoimmune diseases, such as MS.
Krabbe disease (or globoid cell leukodystrophy)	Krabbe disease is caused by a deficiency of galactocerebrosidase - an essential enzyme for myelin metabolism. Krabbe disease is a rare, degenerative disorder of the central and peripheral nervous systems that is characterised by the presence of globoid cells (cells that have more than one nucleus) in demyelinated portions of the brain. Infants with Krabbe disease are normal at birth. Symptoms begin between the ages of 3 and 6 months with irritability, inexplicable crying, fevers, limb stiffness, seizures, feeding difficulties, vomiting, and slowing of mental and motor development. There are also juvenile- and adult-onset cases of Krabbe disease, which have similar symptoms but slower progression. Birth rate is around 1:10,000.
Leukodystrophy	Leuko (Greek meaning: white), Dys (Greek meaning: ill), Trophy (Greek meaning: growth). A group of genetic disorders characterised by the imperfect development or maintenance of myelin. Each Leukodystrophy is caused by genetic defects in how myelin produces or metabolises chemicals and the defect is in a gene that controls one and only one of the chemicals (click here for a list of currently known Leukodystrophies).
Lorenzo's Oil	Used as a therapy for Adrenoleukodystrophy, it is a 4:1 mix of oleic acid and erucic acid, extracted from olive oil and rapeseed oil, respectively. Recent Scientific study showed the possibility of over 74% chance of not developing the ALD symptoms if taking Lorenzo's Oil prior to symptoms arising. Lorenzo's Oil is only affective for ALD and AMN - not any other demyelinating diseases.
Metachromatic Leukodystrophy (MLD)	An inherited disease in which the lack of an enzyme, Arylsufatase-A (ASA), causes the accumulation of sulfatide deposits in the brain, which in turn leads to myelin breakdown. There are 3 forms: Infantile, Juvenile and Adult MLD. Infantile is the most common form usually, with symptoms manifesting around 12-18 months age. Symptoms become progressive and include: low muscle tone (hypotonia), loss of ability to walk and eventually sit on one's own, speech abnormalities, involuntary eye movement (nystagmus), loss of cognitive (mental) abilities, blindness, loss of ability to swallow, convulsions and eventually becoming completely bedridden and unable to communicae. These children are not in a vegetative state, as their intelligence is intact, they have just lost the ability to send any signals from the brain. Life expectancy for Infantile is usually 2-10 years of age. Juvenile MLD usually manifests itself in behaviour challenges and dementia, followed by the same symptoms as Infantile, although slower in its progression Adult MLD appears around age 30 with mental disturbances and progressive dementia, usually running a longer course of about 15 years from first symptoms. Adult MLD persons are not expected to live past middle age. MLD is an auto-recessive disease, which means both parents are carriers of the defective gene and every time they have a child, there is a 1:4 chance they will have an affected child and 2:4 (or 50/50) chance their child will be a carrier and 1:4 chance of non-affected, non-carrier child. Birth rate is about 1:40,000.
Magnetic Resonance Imaging (MRI)	An acronym for magnetic resonance imaging, a non-invasive method of obtaining images of internal soft bodily tissue such as the brain and the spinal cord through the use of powerful magnets and radio waves.
Multiple Sclerosis (MS)	Multiple sclerosis: A disorder of the central nervous system of unknown cause in which the body's immune system attacks myelin in the brain and spinal cord. Whether the disease manifests in repeated episodes of inflammation or as a chronic condition, it results in multiple scars, or scleroses, on the myelin sheath, leading to impairment or loss of nerve function. MS is not currently considered hereditary although you may be more susceptible if there is a family history of MS. There are four recognised forms of MS: Beign MS - episode(s) appeared to lead to diagnosis but there is not a repetition of episodes or they are few and infrequent; Relapsing/Remitting MS - episodes manifest themselves with some residual affect, but usually subside or go into remission and function is restored; Progressive MS - episodes lead to loss of function and/or other symptoms that do not regain or very little, after a period of time; Secondary Progressive MS - the most aggressive form, with faster declination in abilities or rapid onset of symptoms with no regain of function. Currently, there is believed to be about 90,000 people in the UK affected by MS.
Myelin	The fatty sheath coating the axons of the nerves; it allows efficient conduction of nerve impulses. Myelin is produced by oligodendrocytes in the CNS and by Schwann cells in the peripheral nervous system. Myelin, which lends its colour to the "white matter" of the brain, is a complex substance made up of at least ten different chemicals.
Myelin Diseases	Diseases that attack myelin preferentially. They may attack the CNS myelin (as in Multiple Sclerosis and the Leukodystrophies) or the peripheral nervous system (PNS) myelin (as in Guillain-Barre syndrome). While PHS myelin tends to mend itself, CNS myelin does not grow back spontaneously
Myelin Project Work Group	World-class laboratories/Researchers and Specialists with the common goal of developing strategies/therapies for myelin repair. This Workgroup conform to The Myelin Project ground rules, e.g., co-operation rather than competition, teamwork, joint experiments, immediate exchange of information, applied rather than basic research
Nerve	A cordlike structure made up of nerve fibres that conduct impulses to and from the CNS and other parts of the body.
Neural Precursor Cells	Cells with the potential to differentiate into neurons, astrocytes, and oligodendrocytes and to renew themselves
Neuron	The main actors in the brain, neurons are cells that issue and receive electrical signals to and from other parts of the body, and control all functions in humans and animals. Signals to other parts of the body are carried by axons (see Axon).
Olfactory Ensheathing Cells	Cells that ensheathe axons in the nerve that transmits the sense of smell to the brain. Recent studies show that these cells, when transplanted, can remyelinate CNS axons
Oligodendrocytes	Type of glial cell that populates the CNS and is responsible for producing CNS myelin
Oligodentrocyte Precursors (OPs)	Glial cells at a very early stage of development, destined to differentiate into oligodentrocytes
Oncogenea	Any of several genes that control cell growth, division, and normal cell death, which can become mutated and cause cells to grow out of control, leading to cancer. These genes can be used to maintain stem cells as a self-renewing cell line in culture.
Pelizaeus-Merzbacher Disease	A disorder caused by an impairment of the gene coding for a myelin protein, resulting in dysmyelination
Peripheral Nervous System (PNS)	All nerves other than those belonging to the CNS
Presymptomatic	Having a disease, but prior to the appearance of symptoms.
Progesterone	A female steroid hormone secreted by the ovary; it is produced by the placenta in large quantities during pregnancy.
Receptor	The point on the surface or interior of a cell to which a particular molecule, chemical or virus binds
Schwann Cells (SCs)	Glial cells that myelinate the peripheral nervous system
Sclerosis	Literally, "scar"; the hardening of tissue. In multiple sclerosis it refers to the body's replacement of lost myelin around axons with scar tissue
Stem Cells	Cells that can give rise to other types of cells; they are produced both during embryonic development and in the adult body. Embryonic stem cells begin with the ability to become any cell type, and quickly differentiate into cells committed toward a certain type of tissue, e.g., blood, skin, or neural stem cells. These are termed multipotential stem cells, because they further divide into cells with a particular function, such as red and white blood cells and platelets. Multipotential cells are also present in adults. Stem cells are capable of dividing for indefinite periods in culture.
Stereotaxis	A type of brain surgery that uses a system of three-dimensional co-ordinates to locate the site to be operated on
Translational research	Intended to translate knowledge derived from laboratory work (basic research) into clinical applications.
Transverse Myelitis	An inflammation of the spinal cord, sometimes associated with demyelination and paralysis.
Umbilical cord blood stem cell	Blood stem cells left within the umbilical cord post-partum, which can be collected and preserved; they are an alternative to cells from bone marrow for transplantation in a variety of disorders.
Vector	A carrier, or vehicle, that transfers a substance from one host to another. In gene therapy, a disabled virus is commonly used as a means of efficiently inserting genetic material, such as the code for a normal gene, into the body, because viruses can infect most cells.
Ventricles	The four connected cavities of the brain that contain cerebrospinal fluid. Ventricles also refer to two of the chambers of the heart.
Very long chain fatty acids (VLCFA)	Compounds with a long hydrocarbon chain; because of a defective gene and the malfunction of the corresponding enzyme, they accumulate in adrenoleukodystrophy.
X-linked	A trait or disease tied to genes on the X chromosome, which is one of the sex chromosomes that determine gender of an organism. Males have one X and one Y chromosome, while females have two X's. Thus if a defective gene that is X-linked is passed on by one parent to a female child, she will become a carrier, but in many cases will not develop symptoms, because the other gene is normal. When a defective X-linked gene is inherited by a boy, he typically will develop symptoms, because there is only one gene to do the job
Zellweger Syndrome	Disorders such as Zellweger Syndrome, Infantile Refsum's Disease (IRD) and Neonatal ALD (NALD) that are a result from defects in the assembly of cellular structures called the peroxisome.