Glossary

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ALS (amyotrophic lateral sclerosis)
A chronic, progressive disease marked by gradual degeneration of the nerve cells in the central nervous system that control voluntary muscle movement. The disorder causes muscle weakness and atrophy; symptoms commonly appear in middle to late adulthood, with death in two to five years. The cause is unknown, and there is no known cure. Also called Lou Gehrig's Disease, or Motor Neuron Disease. Literally, amyotrophic lateral sclerosis means without muscle nourishment, side (of spinal cord) hardening.

Alzheimer's Disease
A form of degenerative brain disease resulting in progressive mental deterioration with disorientation, memory disturbance and confusion. Alzheimer's leads to progressive dementia, often accompanied by dysphasia and/or dyspraxia. The condition may also give rise ultimately to spastic weakness and paralysis of the limbs, epilepsy and other variable neurological signs.

amino acid
One of the 20 building blocks of protein.

antibody
A defense protein that binds to foreign molecules to allow elimination of the foreign molecule.

antigen
Substances that are capable of causing the production of antibodies. Antigens may or may not lead to an allergic reaction.

antioxidant
A chemical compound or substance that inhibits oxidation.

assay
A method to analyze or quantify a substance in a sample. An assay is an analysis done to determine: 1. The presence of a substance and the amount of that substance. 2. The biological or pharmacological potency of a drug.

atrophy
The progressive loss of muscle mass, or wasting, caused by reduction in the size or number of muscle cells. It is one of the later symptoms of ALS.

autoimmune disease
A disease in which the body produces an immunogenic (i.e., immune system) response to some constituent of its own tissue. In other words the immune system loses its ability to recognize some tissue or system within the body as "self" and targets and attacks it as if it were foreign. Autoimmune diseases can be classified into those in which predominantly one organ is affected (e.g., hemolytic anemia and anti-immune thyroiditis), and those in which the autoimmune disease process is diffused through many tissues (e.g., systemic lupus erythematosus). For example, multiple sclerosis is thought to be caused by T cells attacking the sheaths that surround the nerve fibers of the brain and spinal cord. This results in loss of coordination, weakness, and blurred vision.

axon
The long, hairlike extension of a nerve cell that carries a message to the next nerve cell.

BDNF
Type of growth factor

bioassay
Determination of the potency or concentration of a compound by its effect upon animals, isolated tissues, or microorganisms, as compared with an analysis of its chemical or physical properties.

biochemistry
The chemistry of biology; the application of the tools and concepts of chemistry to living systems. Biochemists study the structures and physical properties of biological molecules.

bioinformatics
The process of developing tools and processes to quantify and collect data to study biological systems logically.

blood-brain barrier (BBB)
A protective barrier formed by the blood vessels and glia of the brain. It prevents some substances in the blood from entering brain tissue.

bulbar
Bulbar ALS is the type that begins with the facial muscles, speech and swallowing.

bulbar muscles
The muscles that control the speech, chewing and swallowing

CD14
A cell marker on bone marrow derived cells

central nervous system (CNS)
The brain and spinal cord combined.

cerebellum
The portion of the brain in the back of the head between the cerebrum and the brain stem. It is responsible for the coordination of movement and balance.

cerebro-spinal fluid (CSF)
A watery fluid, continuously produced and absorbed, which flows in the cavities within the brain and around the surface of the brain and spinal cord.

cerebro spinal fluid analysis (spinal tap)
A procedure used to isolate cerebrospinal fluid for evaluation or diagnosis of disease.

chromosome
A visible carrier of the genetic information.

chronic
Marked by long duration or frequent recurrence.

clodronate
A drug used to deplete macrophages.

CNTF (Ciliary Neurotrophic Factor)
A type of growth factor

cord blood
Blood taken from the umbilical cord at the time of birth. It is rich in a variety of stem cells.

cortex
The outer layer of the cerebrum, densely packed with nerve cells.

CREB
A gene involved in learning and memory. It appears to be the master switch that activates a number of growth factors and potentially some anti-apoptotic genes. Recent studies suggest CREB is neuroprotective.

CSF
See cerebrospinal fluid.

CTLA4
cell marker on the surface of some immune cells.

dementia
Not a disease itself, but group of symptoms that is characterized by a decline in intellectual functioning that is severe enough to interfere with the ability to perform routine activities.

dendrite
Extensions from the neuron cell body that take information TO the cell body. A single nerve may possess many dendrites.

DNA
One of two types of molecules that encode genetic information

dysphagia
Difficulty in swallowing.

Enzyme
A protein that acts as a catalyst in mediating and speeding a specific chemical reaction.

excitotoxic
Exciting neurons which can over time lead to neuronal death.

FDA
U.S. Food and Drug Administration, the branch of federal government which approves new drugs for sale.

FDA 2000
FDA 2000 project is a library of FDA approved compounds based on assay studies completed by Steve Gullans at Harvard.

familial ALS
Approximately 5-10% of all cases of ALS are believed to be familial, occurring in clusters of families in which a large number of individuals are affected. The onset of familial MND tends to be earlier than in sporadic ALS.

fasciculation
Small, involuntary, irregular, visible contractions of individual muscle fibers. Often seen in the legs, arms and shoulders of PALS.

formulation chemistry
Formulation is a process by which a compound is prepared in a suitable form for administration to animals or human being depending on the dose, route and target tissue.

free radicals
Chemicals that are highly reactive and can oxidize other molecules (i.e. Superoxide).

functional genomics
Functional genomics is the area of genetics that focuses on determining the function of genetic information present in a cell or its �genome function".

GDNF (Glial Derived Neurotrophic Factor)
GDNF is a naturally occurring growth factor that proved capable of protecting and promoting the survival of motor neurons in animal studies. A growth factor is a growth inducing protein found in the human body. There was a growing interest in these naturally occurring proteins that have a supportive, reparative or protective role for motor neurons in animals.

Gehrig, Lou
(1903-1941), American professional baseball player, also known as the Iron Horse because he established a record fro the most consecutive games played by a professional baseball player, appearing in 2130 games from 1925 to 1939. From 1923 until 1939 he played first base for the New York Yankees of the American League (AL). Gehrig was twice voted the league's most valuable player (MVP). Stricken with the spinal disease ALS, which later became known as Lou Gehrig's disease, he retired from baseball in 1939.

gene
Genes are the basic biological units of heredity. They are composed of DNA.

gene chip
Gene chips are a way of automating experiments that previously could only be done one at a time. They are a picture of what the RNA looks like at one particular moment. Thousands of DNA pieces in genes are spotted on a small surface enabling us to look at changes in gene expression profile of thousands of genes in one experiment. By comparing tissue from ALS patients with tissue from controls we can discover which genes vary their expression level in the disease.

genome
All of the genetic information; the entire genetic complement; all of the hereditary material possessed by an organism.

glutamate
Glutamate is one of the most common amino acids found in nature. It is the main component of many proteins, and is present in most tissues. Glutamate is also produced in the body and plays an essential role in human metabolism. It is a primary excitatory neurotransmitter in the human CNS, L-glutamate is present at a majority of synapses. Over-stimulation of these same receptors is thought to trigger the neuronal damage associated with a wide variety of neurological insults and diseases, including amyotrophic lateral sclerosis, lathyrisms, and Alzheimer's disease.

glutamate toxicity
Toxicity resulting from excess glutamated synapse.

growth factor
A naturally occurring protein chemical that stimulates cell division differentiation and proliferation. It is produced by normal cells during embryonic development, tissue growth and wound healing.

hydrogen peroxide assay
This assay is used to identify neuroprotective changes that can shield neurons from Hydrogen Peroxide injury.

IgG (Intrathecal Gamma Globulin)
A class of antibody.

IL3 (interleukin-3)
Small proteins released by cells that play a role in bone marrow cell proliferation and differentiation.

immune
Free from acquiring a certain infectious disease; resistant to an infectious disease.

immune system
A complex system that is responsible for distinguishing us from everything foreign to us, and for protecting us against infections and foreign substances. The immune system works to seek and kill invaders.

immunology
The study of all aspects of the immune system including its structure and function, disorders of the immune system, blood banking, immunization and organ transplantation.

immunosuppression
Prevention or interference with the development of an immunologic response; may reflect natural immunologic unresponsiveness (tolerance); may be artificially induced by chemical, biological, or physical agents, or may be caused by disease.

incidence
The occurrence of new cases of a condition. The incidence rate describes the frequency with which cases are identified. Incidence is commonly measured in new cases per 1,000 (or 100,000) of population at risk, per year. The incidence of ALS typically varies between 1 and 4 diagnoses per 100,000 of populations per year in Western nations.

inflammation
The nonspecific immune response that occurs in reaction to any type of bodily injury. It is a stereotyped response that is identical whether the injurious agent is a pathogenic organism, foreign body, ischemia, physical trauma, ionizing radiation, electrical energy or extremes of temperature. The reactions produced during inflammation and repair may be harmful (i.e. hypersensitivity reactions, the processes that lead to rheumatoid arthritis, and possibly microglial over activation in ALS).

inflammatory disease
Diseases that are characterized by activation of the immune system to abnormal levels that lead to disease.

intrathecal
Injection into the innermost membrane surrounding the central nervous system. Usually done by lumbar puncture.

irradiate
To expose a structure or organism to radiation.

ligase
In genetics, the general term for a class of enzymes that speed up the joining of the ends of two chains of DNA.

ligation
The application of a band or bandage.

limb-onset
Refers to the type of ALS where initial symptoms appear in the limbs. The most common form of ALS, the other type being bulbar-onset.

liposome encapsulated clodronate
A macrophage toxin. It is designed so that macrophages will consume it and die.

lower motor neuron
Nerve cells starting at the spinal cord or brain stem and ending at the muscle fibers. The loss of lower motor neurons leads to weakness, twitching of muscles (fasciculations), and loss of muscle bulk (atrophy).

lumbar puncture
A lumbar puncture or "LP" is a procedure whereby spinal fluid is removed from the spinal canal for the purpose of diagnostic testing. It is particularly helpful in the diagnosis of inflammatory diseases of the central nervous system, especially infections, such as meningitis. It can also provide clues to the diagnosis of stroke, spinal cord tumor and cancer in the central nervous system.

macrophage
A type of white blood that ingests (takes in) foreign material. Macrophages are key players in the immune response to foreign invaders such as infectious microorganisms.

magnetic resonance imaging (MRI)
A non-invasive procedure that produces a two-dimensional view of an internal organ or structure, especially the brain and spinal cord.

microglia
Microglia are macrophages derived from bone marrow. They migrate to the CNS during development where they become trapped after the blood brain barrier forms. Microglia are normally inactive but become activated in response to antigenic stimulation. Once activated, they proliferate and migrate to the site of injury where they bind to antigens by using the molecules on their surface. They produce the toxic cytokins IL-1 and TNFalphan when activated. They are major phagocytes, but are located in the central nervous system.

mitochondria
The mitochondria are the principal energy source of the cell. Mitochondria convert nutrients into energy as well as doing many other specialized tasks.

mitochondrial dysfunction
For ALS, cellular energy production is low in motor neurons. Excessive free radical activity appears to be caused by deficiencies in cellular energy production which is a function normally carried out by mitochondria.

molecule
The smallest unit of a substance that can exist alone and retain the character of that substance.

motor neuron disease (MND)
A group of disorders in which motor nerve cells (neurons) in the spinal cord and brain stem deteriorate and die. ALS is the most common motor neuron disease.

motor neuron
A neuron that conveys impulses initiating muscle contraction or glandular secretion.

muscle
Muscle is the tissue of the body which primarily functions as a source of power. There are three types of muscle in the body. Muscle which is responsible for moving extremities and external areas of the body is called "skeletal muscle." Heart muscle is called "cardiac muscle." Muscle that is in the walls of arteries and bowel is called "smooth muscle."

muscle atrophy
Loss of muscle fiber volume characterized by a visible decrease in muscle size. This occurs because muscles no longer receive impulses or signals from nerve cells.

multiple sclerosis (MS)
A chronic degenerative disease of the central nervous system in which gradual destruction of myelin occurs in patches throughout the brain or spinal cord (or both), interfering with the nerve pathways and causing muscular weakness, loss of coordination and speech and visual disturbances. It occurs chiefly in young adults and is thought to be a defect in the immune system that may be of genetic or viral origin.

mutation
A permanent change, a structural alteration, in the DNA or RNA. Mutations can be caused by many factors including environmental insults such as radiation and mutagenic chemicals. Mutations are sometimes attributed to random chance events.

nerves
A bundle of fibers that uses electrical and chemical signals to transmit sensory and motor information from one body part to another..

nervous system
The system of cells, tissues and organs that regulates the body's responses to internal and external stimuli. In vertebrae it consists of the brain, spinal cord, nerves, ganglia and parts of the receptor and effector organs.

neuroimmune
In the microglial theory of ALS, the inflammatory immunological response to CNS injury causes damage in ALS. If this theory is correct, it could be said that ALS is a neuroimmune disease.

neurologist
A physician who specializes in the nervous system and its disorders.

neurology
The medical science that deals with the nervous system and disorders affecting it.

neuromuscular
Of, relating to, or affecting both nerves and muscles.

neuron
Neurons are the nerve cells which make up the central nervous system. They consist of a nucleus, a single axon which conveys electrical signals to other neurons and a host of dendrites which deliver incoming signals.

neuronal receptors
Neurons use chemical signaling mechanisms to communicate with one another. These impulses are transmitted at specialized junctions called synapses. The sending or signaling neuron triggers the release of neurotransmitters (or chemicals) into the synaptic cleft. From there the transmitters bind to receptors on the post synaptic or receiving neuronal cell. These receptors are the gate keepers of neuronal cells and they open and close to send or receive chemicals that signals which direct the actions and reactions of the cell. Chemical synapses can be excitatory or inhibitory. In an inhibitory synapse, binding of the neurotransmitter causes a change in ion permeability that tends to block the generation of opening of the plasma membrane in the receiving cell. For most cases, the binding of an inhibitory neurotransmitter causes a hyper polarization in closing of the postsynaptic or receiving membrane.

neuroprotective
If an agent provides protection to any part of the body's nervous system, it is said to provide neuroprotection.

neuroregenerative
If an agent provides growth and regeneration to any part of the nervous system, it is said to be neuroregenerative.

neuroscience
The scientific disciplines concerned with the development, structure, function, chemistry, pharmacology, clinical assessments and pathology of the nervous system.

neurotransmitters
Chemical substances that carry impulses from one nerve cell to another; found in the space (synapse) that separates the transmitting neuron's terminal (axon) from the receiving neuron's terminal (dendrite).

onset
The time of appearance of the first symptoms of a condition, prior to seeking diagnosis.

oxidative stress
Accumulation of destructive molecules called free radicals can lead to motor neuron death. Free radicals damage components of the cells' membranes, proteins or genetic material by "oxidizing" them-the same chemical reaction that causes iron to rust. Some patients with familial ALS have mutations in the gene for superoxide dismutase type 1 (SOD1). SOD1 normally breaks down free radicals, but mutant SOD1 is unable to perform this function. These free radicals may be generated when the enzyme superoxide dismutase malfunctions (either because of a genetic mutation or because of the chemical environment of the nerve cells), or they may be generated as a result of glutamate excitotoxicity, or for some other reason. Many ALS patients take over the counter antioxidants such as Coenzyme Z Q10 and Vitamin E in an effort to neutralize free radicals.

PALS
Person with ALS.

Parkinson's Disease
The most common form of Parkinson's is slowly progressing and degenerative, usually associated with the following symptoms. All of these result from the loss of dopamine-producing brain cells: tremor or trembling of the arms, jaw, legs, and face; stiffness or rigidity of the limbs and trunk; bradykinesia � slowness of movement; postural instability, or impaired balance and coordination.

phagocyte
A cell that can engulf particles such as bacteria, other microorganisms, aged red blood cells, foreign matter, etc.

pharmacokinetics
The study of the metabolism and action of drugs with particular emphasis on the time required for absorption, duration of action, distribution in the body and method excretion.

pharmacology
The study of drugs and their origin, nature, properties and effects upon living organisms.

pharmacological properties
A drug's half life, molecular weight, permeability, chemical structure and methods of action through the pathways it affects.

phenotype
The expression of the genes present in an individual. This may be directly observable (eye color) or apparent only with specific tests (blood type). Some phenotypes such as the blood groups are completely determined by heredity, while others are readily altered by environmental agents.

plasmid
A self-replicating (autonomous) circle of DNA distinct from the chromosomal genome of bacteria. A plasmid contains genes normally not essential for cell growth or survival. Some plasmids can integrate into the host genome, be artificially constructed in the laboratory and serve as vectors (carriers) in cloning.

primary lateral sclerosis (PLS)
A progressive neurological disease in which the upper motor nerve cells deteriorate. If the lower motor neurons are not affected within two years, the disease usually remains a purely upper motor disease.

protein
Proteins are large molecules required for the structure, function, and regulation of the body's cells, tissues, and organs. Each protein has unique functions. Proteins are essential components of muscles, skin, bones and the body as a whole. Protein is also one of the three types of nutrients used as energy sources by the body.

protocol
A precise and detailed plan for the study of a biomedical problem or for a regimen of an experimental therapy.

radiation
Rays of energy. The term "radiation" also refers to the use of energy waves to diagnose or to treat disease.

Rilutek
The only FDA-approved drug available to treat ALS. It inhibits glutamate release, and prolongs life approximately three months. Riluzole is the generic name of Rilutek.

RNA
A long-chain, usually single-stranded. The primary function of RNA is protein synthesis within a cell. However, RNA is involved in various ways in the processes of expression and repression of hereditary information. The three main functionally distinct varieties of RNA molecules are: (1) messenger RNA (mRNA) which is involved in the transmission of DNA information, (2) ribosomal RNa (rRNA) which makes up the physical machinery of the synthetic process, and (3) transfer RNA (tRNA) which also constitutes another functional part of the machinery of protein synthesis.

routes of administration
The different ways in which a drug can be delivered (i.e. intravenously, intrathecally, intramuscularly, pill form (orally)).

serotonin
An important neurochemical whose effects upon the human brain include mood elevation. Production of serotonin in the brain is increased by ingestion of the amino acid tryptophan (a chemical precursor to serotonin) and the pharmaceutical anti-depressant Prozac (trademarked product of Eli Lilly & Company). In 1997, Marianne Regard and Theodor Landis discovered that humans afflicted with hemorrhagic lesions in the brain (cause of abnormal serotonin activation/production) often became "passionate culinary afficionados."

sclerosis
A hardening within the nervous system, especially of the brain and spinal cord, resulting from degeneration of nervous elements such as the myelin sheath.

side effect
An action or effect of a drug other than that desired. Commonly it is an undesirable effect such as nausea, headache, insomnia, acute toxic reaction or drug interaction.

SOD
See superoxide dismutase.

SOD assay
Bob Brown at Massachusetts General Hospital is completing this project. The SOD assay uses the mutant SOD gene and a series of drugs that are presented to the SOD cells that attempt to prevent the cells' death. He has screened approximately 400 drugs and has had 14 hits thus far. This assay testing is still in progress.

spinal cord
Part of the central nervous system extending from the base of the skull through the vertebrae of the spinal column. It is continuous with the brain stem, and like the brain it is encased in a triple sheath of membranes. Thirty-one pairs of spinal nerves arise from the sides of the spinal cord. The spinal cord carries information from the body's nerves to the brain and signals from the brain to the body.

stem cells
Cells that can differentiate into many different cell types when subjected to the right biochemical signals. Stem cells are a promising new therapeutic approach to treating CNS disorder. The most versatile stem cells, called pluripotent stem cells, are present in the first days after an egg is fertilized by sperm. Researchers believe they can coax stem cells to become whatever tissues patients need. Stem cells come from embryos, bone marrow and umbilical chords.

stem cell transplant
Transplantation of stem cells from various sources has provided improvement in animal spinal neurodegenerative disease models such as stroke, epilepsy, Parkinson's and spinal cord injury. Human trials are promising, but not complete.

stroke
Also called a "brain attack" and happens when brain cells die because of inadequate blood flow. 20% of cases are a hemorrhage in the brain caused by a rupture or leakage from a blood vessel. 80% of cases are also know as a "schemic stroke", or the formation of a blood clot in a vessel supplying blood to the brain.

superoxide dismutase
An enzyme that destroys superoxide. One form of the enzyme contains manganese and another contains zinc. Superoxide is a highly reactive form of oxygen. For ALS, 20% of the total population of patients have mutations in the gene for copper/zinc superoxide dismutase type SOD1. SOD1 normally breaks down free radicals, but mutant SOD1 is unable to perform this function.

synapse
A tiny gap between the ends of nerve fibers across which nerve impulses pass from one neuron to another; at the synapse, an impulse causes the release of a neurotransmitter, which diffuses across the gap and triggers an electrical impulse in the next neuron.

therapeutic index
A general way of measuring an effective dose of a drug and its toxicity.

transgenic
An organism whose sperm or egg contain genetic material originally derived from an organism other than the parents or in addition to the parental genetic material.

treatment
Medical or surgical management of a patient. Any specific procedure used for the cure of or the amelioration of a disease or pathological condition.

tremor
A rhythmical shaking of a limb, head, mouth, tongue or other part of the body that is involuntary in nature.

toxicity
The extent, quality or degree of being poisonous.

toxicology
Division of medical and biological science concerned with drugs. Scientists study their chemistry and pharmacological actions, and establish antidotes and treatment of toxic manifestations, prevention of poisoning, and methods for controlling exposure to harmful substances.

toxin
A poisonous substance of animal or plant origin.

upper motor neurons
Nerve cells (neurons) originating in the brain's motor cortex and running through the spinal cord.

vaccine
Any substance, bearing antigens on its surface, that causes activation of an animals' immune system without causing actual disease. The animals' immune system components (e.g. antibodies) are then prepared to quickly vanquish those particular pathogens when they later enter the body.

vector
The agent used (by researchers) to carry new genes into cells. Plasmids currently are the vectors of choice, though viruses and other bacteria are increasingly being used for this purpose.

Wobbler
Wobbler is a neurodegenerative disease model that arose in a laboratory mouse by chance. As it has a very valuable phenotype that mimics ALS and other motor neuron diseases, it was maintained by breeding. As it was a mutation that arose spontaneously, we currently have no information on where in the mouse genome the ALS-producing mutation is present. Currently investigators are trying to identify the location of the mutation in the mouse. Various therapies have been tested in this model and most of the drugs that worked in the model also worked in the genetic ALS model (SOD1G93A). Thus it appears that this is a good model for screening drugs.

zVAD-FMK
A drug that extended the life of ALS mice by 21 percent. Studies concluded that although zVAD-FMK helps mice, the drug is too toxic for human use. It's a caspase (cell suicide) and protease (enzymes that cut proteins to shreds for recycling) inhibitor and ALSTDF is now collaborating in the development of safer drugs that affect the same pathways. There are two new versions of zVAD-FMK that are now in formulation testing at the Institute.

ALS Therapy Development Institute compiled this glossary from the following sources:

ALS Survival Guide
www.biotechterms.org
www.MedTerms.com

ALSTDF thanks the above sources for the use of their terms.


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