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 is the most common cause of dementia afflicting 24 million people worldwide. 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. In its most common form, it occurs in people over 65 years old. The duration of the disease is estimated between 5 and 20 years. There is no known cure.

A group of 20 building blocks that make up proteins. Proteins are defined by their unique sequence of amino acids. Just as the letters of the alphabet can be combined to form an almost endless variety of words, amino acids can be linked in varying sequences to form a vast variety of proteins.

Also known as immunoglobulins, they are gamma globulin proteins that are found in blood or other bodily fluids, and are used by the immune system to identiy and neutralize objects such as bacteria and viruses.

An antigen or immunogen is a substance that prompts the generation of antibodies and can cause an immune response.

A chemical compound that is capable of slowing or preventing the oxidation of other molecules.

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.

The progressive loss of muscle mass, or wasting, caused by reduction in the size or number of muscle cells. Causes include poor nurishment, poor circulation, loss of hormonal support loss of nerve supply, lack of exercise, and disease. It is one of the later symptoms of ALS.

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.

A long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body. Axons are in effect the primary transmission lines of the nervous system, and as bundles they help make up nerves.

Back to Top

Brain-Derived Neurotrophic Factor is a type of growth factor found in the brain. It is a protein that acts on certain neurons of the central and peripheral nervous system that helps to support the survival existing neurons and encourage the growth and differentiation of new neurons and synapses.

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.

This is the study of the chemical processes in living organisms. It deals with the structure and function of cellular components such as proteins, carbohydrates, lipids, nucleic acidds, and other biomolecules.

This involves the use of techniques including applied mathematics, informatics, statistics, computer science, artificial intelligence, chemistry, and biochemistry to solve biological problems usually on the molecular level.

A protective barrier formed by the blood vessels and glia of the brain. It prevents some substances in the blood from entering brain tissue and makes drug-targeting to the CNS more challenging than other tissues.

Patients with ALS generally present with symptoms referable either to the limb or bulbar muscles. Bulbar complaints will consist of difficulty with speech and swallowing. Muscles of the throat, tongue, jaw, and face are known as bulbar because the are of the brain that controls them was once known as the bulb.

The muscles of the throat, tongue, jaw, and face which control speech, chewing, and swallowing. The lower brain stem, once known as the bulb, controls these muscles, and just like motor neurons in the spinal cord, can degenerate and die in ALS. This results in weakness or wasting of the bulbar muscles. About 25% of ALS patients begin their disease with bulbar onset.

Back to Top

A cell marker on bone marrow derived cells.

Consisting of the brain and spinal cord, it contains the majority of the nervous system.

It is a region of the brain that plays an important role in the integration of sensory perception and motor control. There are many neural pathways linking the cerebellum with the res of the CNS. The cerebellum integrates these pathways like a train conductor, using the constant feedback on body position to fine tune motor movements.

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. It acts like a "cushion" or buffer.

Also known as a lumbar puncture, it is a diagnostic procedure that is performed in order to collect a sample of cerebro-spinal fluid for evaluation and study.

They are organized structures of DNA and proteins that are found in cells. A continuous piece of DNA, it contains many genes.

In medicine, a chronic disease is a disease that is long-lasting or recurrent. The term chronic describes the rate of onset and development.

Clodronate is a medicine used to treat a high level of calcium in the blood caused by changes in the body that happen with cancer. Clodronate also treats the weakening in the bones when cancer has spread to the bones from another part of the body.

Ciliary Neurotrophic Factor is a human gene. The protein is a potent survival factor for neurons and may be relevant in reducing tissue destruction during inflammatory attacks.

Blood taken from the umbilical cord at the time of birth - it is rich in certain stem cells.

The cerebral cortex is a structure within the brain that plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. The human cerebral cortex is 2-4mm thick.

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.

(See cerebrospinal fluid.)

A cell marker with a comparatively higher binding affinity that has made it a potential therapy for autoimmune diseases. It plays a role in the initial immune response to and infection of immune cells.

Back to Top

This is the progressive decline in cognitive function due to damage or diease in the brain beyond what might be expected from normal aging. Affected areas in cognition may be memory, attention, language, and problem solving. Especially in the later stages of the condition, affected persons may be disoriented in time, place, and person.

These are the branched projections of a neutron that act to conduct the electrical stimulation received from other neural cells to the cell body. They play a critical role in integrating synaptic inputs.

A Diaphragm Pacemaker is a phrenic nerve stimulator that provides pacing ventilatory support for patients with chronic respiratory insufficiency, or whose diaphragm, lungs, and phrenic nerves have decreased function. Patients in need of a diaphragmatic pacemaker have high spinal cord injuries, central sleep apnea or other central neurological disorders.

This is the primary molecule that encode genetic information - physically it consists of a long chain of nucleotides and is condensed and packaged through interaction with special proteins to form chromosomes.

Dysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs", the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia.

Back to Top

Enzymes are biomolecules that catalyze, or increase the rates of, chemical reactions. Almost all enzymes are proteins. Almost all processes in a biological call need enzymes in order to occur at significant rates.

This refers to the ability of glutamate or related excitatory amino acids to mediate the death of central neurons under certain conditions, for example, after intense exposure. Such excitotoxic neuronal death may contribute to the pathogenesis of brain or spinal cord injury associated with several human disease states.

Back to Top

The U.S. Food and Drug Administration is an agency of the U.S. Department of Health and Human Services and is responsible for the saftey regulation of most types of food, dietary supplements, drugs, vaccines, biological medical products, blood products, medical devices, radiation-emitting devices, veterinary products, and cosmetics.

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

Approximately 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. Most familial ALS is inherited as a dominant mutation which implies approximately half the members of a family will be affected.

Also called a "muscle twitch", it is a small, local, involuntary muscle contraction visible under the skin arising from the spontaneous discharge of skeletal muscle fibers. Fasciculations have a variety of causes, the majority of which are benign, but can also be due to disease of the motor neurons.

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.

In Chemisty, free radicals are atomic or molecular species with unpaired electrons on an otherwise open shell configuration. These unpaired electrons are usually highly reactive, so free radicals are likely to take part in chemical reactions.Free radicals play an important role in combustion, atmospheric chemistry, polymerization, plasma chemistry, biochemistry, human physiology and many other chemical processes.

This is a field of molecular biology that attempts to make use of the vast wealth of data produced by genomic projects, such as genome sequencing projects, to decribe gene and protein functions and interactions.

Back to Top

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.

(1903-1941), Henry Louis "Lou" Gehrig was an American baseball player in the 1920s and 1930s who set several Major League records and was popularly called "The Iron Horse" for his durability. His record for most career grand slam home runs (23) still stands today. Gehrig was voted the greatest first baseman of all time by the Baseball Writers' Association. A native of New York City, he played for the New York Yankees until his career was cut short by Amyotrophica Lateral Sclerosis (ALS), now commonly referred to in the United States as Lou Gehrig's Disease.

A gene is a locatable region of genomic sequence, corresponding to a unit of inheritance. The physical development and phenotype of organisms can be thought of as a product of genes interacting with each other and with the enviroment.

Gene chips are devices not much larger than postage stamps. They are based on a glass substrate wafer and contain many tiny cells- 400,000 is common. Each holds DNA from a different human gene. They array of cells makes it possible to carry out a very large number of genetic tests on a sample at one time. The hope is that it will soon be possible for doctors to use these devices to run simple tests on patients during examinations in order to diagnose diseases with a genetic base or to find a treatment tailored to an individual's genetic make-up.

In biology the genome of an organism is its whole hereditary information and is encoded in the DNA. An analogy to the human genome stored on DNA is that of instructions stored in a book. 1. The book is over 1 billion words long. 2. The book is bound into 5000 volumes, each 300 pages long. 3. The book fits into a cell nucleus the size of a pinpoint. 4. A copy of the book (all 5000 volumes) is contained in almost every cell.

Gene therapy is the insertion of genes into an individual's cells and tissues to treat a disease. It has been used with some success. In most studies, a "corrected" gene is inserted into the genome to replace and "abnormal" disease-causing gene.

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 also a primary excitatory neurotransmitter in the human CNS, L-glutamate is present at a majority of synapses. Over-stimulation of these same receptors is hypothesized to trigger the neuronal damage associated which could play a role in a wide variety of neurological insults and diseases, including amyotrophic lateral sclerosis, lathyrisms, and Alzheimer's disease.

Toxicity resulting from an excessively glutamate-stimulated synapse.

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.

Back to Top

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

Back to Top

A class of antibody.

Interleukin-3 is a type of biological signal that can improve the body's natural response to disease as part of the immune system. It acts by binding to the Interleukin-3 receptor. It is secreted by activated T cells to support growth and differentiation of T cells from the bone marrow in an immune response.

Immunity is a medical term that desribes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involved both specific and non-specific components. The non-specific components act either as barriers or as eliminators of pathogens to stop infection by micro-organism before they can cause disease. Other components of the immune system adapt themselves to each new disease encountered and are able to generate pathogen-specific immunity.

An immune system is a collection of mechanisms within an organism that protects against disease by identifying and likking pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own healthy cells and tissues in order to function properly. Detection is complicated as pathogens adapt and evole new ways to successfully infect the host organism.

This is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with, among other things, the physiological functioning of hte immune system in states of both health and disease, malfunctions of the immune system in immunologial disorders, and the physical, chemcial and physiological characteristics of the components of hte immune system in vitro, in situ, and in vivo.

This involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions. Deliberately induced immunosuppression is can be done as treatment of other conditions.

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 is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a synonym for infection. The reactions produced during inflammation and repair may be harmful (e.g. hypersensitivity reactions, the processes that lead to rheumatoid arthritis, and possibly microglial over activation in ALS).

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

This is an injection into the intrathecal space surrounding the spinal cord for spinal anaesthesia, chemotheraphy, or pain management applications. This route is also used for some infection. The drug needs to be given this way to avoid the blood brain barrier.

In vivo means that which takes place inside an organism. In science, in vivo refers to experimentation done in or on the living tissue of a while living organism as opposed to a partial or dead one or a controlled enviroment. Animal testing and clinical trials are forms of in vivo research.

This is the process by which an item is exposed to radiation. The exposure can be intentional, sometimes serve a purpose, or it can be accidental.

Back to Top

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

The act of making a ligature or tie. In medicine, a ligature is a device, similar to a tourniquet, usually of thread or string, tired around a limb, blood vessel or similar to restrict blood flow. A ligature can be use for tumor strangulation, carried out before removal.

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.

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

These are the motor neurons connecting the brainstem and spinal cord to muscle fibers, bringing the nerve impulses from the upper motor neurons out to the muscles. Damage to lower motor neurons is indicated by fasciculations, paralysis, weakening of muscles, and neurogenic atrophy of skeletal muscles.

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.

Back to Top

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

Also called an MRI, it is a medical imaging technique primarily used in Radiology to visualize the structure and function of the body. It provides detailed timages of the body is any plane. It has much greater soft tissue contrast than computed tomography (CT) making it especially useful in neurological, musculoskeletal, cardiovascular, and oncological imaging.

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 TNF alpha when activated. They are the major phagocytes located in the central nervous system.

In cell biology, a mitochondrion (plural, mitochondria) is a membrane-enclosed organelle found in most eukaryotic cells. Mitochondria are sometimes described as "cellular power plants" because they generate most of the cell's supply of adenosine triphosphate (ATP) or chemical energy. They are involved in a range of other processes as well, including control of the cell cycle and cell growth. They have been implicated in several human diseases, and may play a role in the aging process.

One hypothesis in ALS is that 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.

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

A group of progressive neurological disorders that destroy motor neurons, the cells that control voluntary muscle activity such as speaking, walking, breathing, and swallowing. ALS is an example. Diagnosis is a clinical one, by a neurologist based on history and neurological examination. There is no diagnostic test. Although an individual's progression may sometimes "plateau", it will not improve.

In vertebrates, the term motor neuron classically applies to neurons located in the central nervous system (CNS) that projects their azons outside the CNS to control muscles.

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."

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.

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.

A permanent change, a structural alteration, in the DNA that encodes the genetics. Mutations can be caused by many factors including environmental insults such as radiation and mutagenic chemicals. Mutations are sometimes attributed to random chance events. They cause variations in the gene pool, eventually getting sorted out or resulting in adaptive evolutionary changes.

Back to Top

A nerve is an enclosed, cable-like bundle of fibers that use electrical and chemical signals to transmit sensory and motor information from one body part to another.

The nervous system is a highly specialized network whose principal components are neurons that coordinate multiple functions in organisms. There are two different systems within the human body, the central nervous system (CNS) and the peripheral nervous system. The CNS is the larger part of the nervous system including the brain and the spinal cord. The PNS consists of all the other nervous structures that do not lie in the CNS.

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.

These are physicians who specialize in neurology, and are trained to investigate, or dignose and treat, neurological disorders. Neurologists may also be involved in clinical research, clinical trials, as well as basic research and translational research.

Neurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue, such as muscle.

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

Neurons are electrically excitable cells in the nervous system that process and transmit information. Neurons are the core components of the brain and spinal cord. They are typically composed of a soma, or cell body, a dendrite and an axon. They communicate via chemical and electrical synapses in a process known as synaptic transmission.

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.

This term refers to mechanisms within the nervous system which protect neurons from degeneration, for example following a brain injury or as a result of chronic neurodegenerative diseases.

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

The scientific disciplines concerned with the development, structure, function, chemistry, pharmacology, clinical assessments and pathology of the nervous system. Neuroscience is at the frontier of investigation of the brain and mind. The study of the brain is becoming the cornerstone is understanding how we perceive and interact with the external world and, in particular, how human experience and human biology influence each other.

They are the chemicals that are used to relay, amplify, and modulate signals between a neuron and another cell. They are found in the space (synapse) that separates the transmitting neuron's terminal (axon) from the receiving neuron's terminal (dendrite).

Back to Top

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

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. Oxidative stress is one hypothesis of a mechanism behind initiation or progression of the disease and some patients take over the counter antioxidants such as Coenzyme Z Q10 and Vitamin E in an effort to neutralize free radicals.

Back to Top

Person with ALS.

Parkinson's disease (PD) is a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills and speech, as well as other functions. Parkinson's disease belongs to a group of conditions called movement disorders. 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. Other typical symptoms include disorders of mood, behavior, thinking, and sensation. Patients' individual symptoms may be quite dissimilar and progression of the disease is also distinctly individual.

A phagocyte is a biological cell that ingests and destroys foreign matter such as microorganisms and debris by a process called phagocytosis. There are three main categories of phagocytes; macrophages, microphages, and dendritic cells. Phagocytes eat pathogens and are extremely useful as an initial immune system response to infection. They engulf pathogens, debris, dead or dying cells and extracellular matric. Phagocytosis is an active process in wound healing.

This is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism. In practice, this discipline is applied mainly to drug substances, though in principle it concerns itself with all manner of compounds ingested or otherwise delivered externally to an organism such as nutrients, metabolites, hormones and toxins. Pharmacokinetics is often divided into several areas; the extent and rate of Absorption, Distribution, Metabolism, and Excretion, or the ADME scheme. It explores what the body does to the drug and is sometimes abbreviated as PK.

This is the study of how drugs interact with living organisms to produce a change in function. If substancs have medicinal properties, they are considered pharmaceuticals. The field encompasses drug composition and properties, interactions, toxicology, therapy, and medical applications and antipathogenic capabilities. Pharmacology is not synonymous with pharmacy, which is the name used for a profession. It deals with how drugs interact within biological systems to affect function.

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

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.

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.

PLS is a rare neuromuscular disease characterized by progressive muscle weakness in the voluntary muscles. It belongs to a group of disorders known as motor neuron diseases. Motor neuron diseases develop when the nerve cells that control voluntary muscle movement degenerate and die, causing weakness in the muscles they control. Onset of PLS usually occurs after age 50. Symptoms may include difficulty with balance, weakness and stiffness in the legs, and clumsiness. Other symptoms may include spasticity (sudden, involuntary muscle spasms) inthe hands, feet, or legs, foot dragging and speech problems due to involvement of the facial muscles. The disorder usually begins in the legs, but it may also start in the tongue or the hands. The disease- which scientists believe is not hereditary- progresses gradually over a number of years, or even decades. In PLS, there is no evidence of the degeneration of the spinal notor neurons or muscle wasting that occurs in ALS. The issue of whether PLS exists as a different entity from ALS is not clear as some patients initially diagnosed as having PLS ultimately develop lower motor neuron signs.

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.

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

An FDA-approved drug for malaria that is being considered as a possible therapeutic to lower mutant SOD1 protein expression in familial ALS patients.

Back to Top

As used in physics, it is energy in the form of waves or moving subatomic particles emitted by an atom or toehr body as it changes from a higher energy state to a lower energy state. Radiation therey (or radiotherapy) is the medical used of ionizing radiation as part of cancer treatment to control malignant cells.

This is the first effective treatment for people with ALS. Laboratory studies suggest that Rilutek is "neuroprotective", which means it protects nerve cells from damage. Many researchers believe that Rilutek protects the nerve cells by what they describe as "glutamate inhibition". Researchers also believe that this activity could explain the effect Rilutek has on the survival of people with ALS. The human body naturally produces glutamate, which carries signals to the motor neurons. This is one link in the chain of how the brain tells the muscles what to do. One of several theories researchers have in that in people with ALS, parts of the nervous system are overexposed to glutamate. A buildup of glutamate "burns out" the motor neurons so that they can't carry the brain's messages to the muscles to tell them what to do.

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.

This is a naturally occuring mechanism that inhibits gene expression. Many organisms utilize RNAi to target and destroy invading viruses, to regulate development, and to maintain their genome. Currently, scientists are trying to develop therapeutics that use this recently discovered mechanism as a means to treat disease.

In pharmacology and toxicology, a route of administration ist he path by which a drug, fluid, poison, or other substance is brought into contact with the body. Obviously, a substance must be transported from the site of the entry into the part of the body where its action is desired to take place. Routes of administration can broadly be divided into topical or local effect (substance is applied directly to whre its action is desired), enteral (desired affect is systematic and substance is given via the digestive tract), or perenteral (desired effect is systematic and substance is given by other routes then the digestive tract).

Back to Top

An important neurochemical synthesized in the cells of the central nervous system and gastrointestinal tract, it is believed to play an important role as a neurotransmitter; in the modulation of anger, aggression, body temperature, mood, sleep, sexuality, and appetites as wellas stimulating vomiting. 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).

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

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.

See superoxide dismutase.

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.

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.

Cells with the special property that allow them to either generate more stem cells or 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 can come from a variety of sources.

A stem cell transplant is the infusion of healthy stem cells into the body. This may be necessary if the bone marrow stops working and doesn't produce enough healthy white blood cells, red blood cells, or platelets. It is also known as a bone marrow transplant or an umbilical cord blood transplant, depending on the source of stem cells.Transplantation of stem cells from various sources has been investigated in animal spinal neurodegenerative disease models such as stroke, epilepsy, Parkinson's and spinal cord injury.

Stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain. This can be due to a lack of bloody supply caused by thrombosis or embolism, or due to a hemorrage. Stroke is a medical emergency and can cause permenant neurological damange, complications and death if not promptly diagnosed and treated. It is the third leading cause of death in the U.S. It is the leading cause of adult disability in the U.S. and Europe. It is the number two cause of death world-wide and may soon become the first. Rist factors include advanced age, hypertension, pervious stroke, diabetes, high cholesterol, and cigarette smoking.

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.

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. They provide the means through which the nervous system connects to and controls the other systems of the body.

Back to Top

Also known as therapeutic ratio, it is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxic effects. A high therapeutic index is preferable to a low one; this corresponds to a situation in which one would have to take a much higher amount of a drug to do harm then the amount taken to do good.

The entire collection of mRNA present in a given cell or groups of cells at any given moment. The analysis of the transcriptome with gene chips provides a snapshot of the cellular biochemistry and can provide insight into molecular mechanisms of pathology.

This is having genetic material (DNA) from another species. This term can be applied to an organism that has genes from another organism. It is understood that the foreign genes are in the transgenic animal's germ-cell DNA and so can be transmitted from one generation to the next.

Translational medicine is a branch of medical research that attempts to more directly connect basic research to patient care. Transaltional medicine is growing in importance in the healthcare industry, and is a term whose precise definition is in flux. The emphasis is on the linkage between the laboratory and the patient's bedside, without a real disconnect. This is often called the "bench to bedside" definition. It can also refer to the development and application of new technologies in a patient driven enviroment- where the emphasis is on early patient testing and evaluation. In modern healthcare, we are seeing a move to a more open, patient driven research process, and the embrace of a more research driven clinical practice of medicine.

In health, treatment is synonymous to therapy, the act of remediation of a health problem, which could include chemotherapy, counseling, pharmacotherapy, and psychotherapy.

Tremor is an unintentional, somewhat rhythmic, muscle movement involving to-and-from movements of one of more parts of the body. It is the most common of all involuntery movements and can affect the hands, arms, head, face, vocal cords, trunk, and legs. In some people, tremor is a symptom of another neurological disorder. It is generaly caused by problems in parts of the brain or spinal cord that control muscles throughout the body or in particular areas. Neurological disorders or conditions that can produce tremor include Multiple Sclerosis, stroke, traumatic brain injury and neurogentitive diseases that damage or destroy parts of the brain stem or cerebellum. Tremor may occur at any age but is most common in middle-aged and older persons. It may be occasional, temporary, or occur intermittently. Tremor affects men and women equally.

This is the degree to which something is able to produce illness or damage to an exposed organism. Toxicity can refer to the effect on a whole organism, such as a human or a bacterium or a plant, or to a substructure, such as a cell or an organ such as a liver. Toxicity is the ability of a chemical or physical agent to induce detrimental temporary or permananet tissue change or to detrimentally interfere with normal biochemical processing.

This is the study of the adverse effects of chemicals on living organisms. It is the study of symptoms, mechanisms, teatments, and detection of poisoning, especially the poisoning of people. Toxicollgy is the study of the relationship between dose and its effects on the exposed organism. The chief criterion regarding the toxicity of a chemical is the dose, or the amount of exposure to the substance.

A toxin is a poisonous substance produced by living cells or organisms that is active at very low concentrations. Toxins can be small molecules, peptides, or proteins and are capable or causing disease on contract or absorption with body tissues by interacting with biological macromolecules such as enzymes or cellular receptors. Toxins cary greatly in their severity, ranging from usually minor and acute (as in a bee sting) to almost immediately deadly.

Back to Top

Upper motor neurons are motor neurons that originate in the motor region of the cerebral cortex or te brain stem and carry motor information down to any motor neurons that are not directly responsible for stimulating the target muscle. These neurons connect the brain to the appropriate level in the spinal cord, from which point nerve signals continue to the muscles by means of the lower motor neurons.

Back to Top

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.

The agent used (by researchers) to carry new genes into cells. The vector itself is generally a DNA sequence that consists of an inset and a larger ssequence that serves of the "backbone" of the vector. The purpose of a vector to transfer genetic information to another cell is typically to isolate, multiply, or express the insert in the target cell. Plasmids currently are the vectors of choice, though viruses and other bacteria are increasingly being used for this purpose.

Back to Top

The Wobbler mouse 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 wa a mutiation that arose spontaneously, we currently have no information on where in the mouse genome that 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. Thus it appears that this is a good model for screening drugs.

Back to Top

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.

Back to Top

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

ALS TDI thanks the above sources for the use of their terms.