Amyotrophic lateral sclerosis, more commonly known as ALS, is a progressive neurodegenerative disease in the central nervous system that impacts the brain and spinal cord, resulting in a loss of muscle control.
It is colloquially referred to as Lou Gehrig’s Disease, after the famous baseball player who battled it in the late 1930s, and does not yet have a cure. To better understand the language of ALS, the ALS Glossary below provides definitions for research terms commonly used by our Innovation Ecosystem and the extended ALS community.
An adeno-associated virus (AAV) vector is the part of a virus able to enter cells, but lacks any of the cell's damaging properties. AAV vectors can be genetically engineered to deliver a gene by selectively "infecting" the cell. AAV vectors have become one of the most common vehicles for gene delivery.
Abnormal proteins do not function as they should and are often produced by genetic mutations. TDP-43 is an example of a protein that becomes abnormal in ALS patients and becomes dysfunctional and clumps.
activities of daily living (ADLs)
The fundamental skills required to independently care for oneself. Basic ADLs include eating, dressing and toileting. Instrumental ADLs include managing transportation, shopping, finances and medications.
ALS (amyotrophic lateral sclerosis)
A progressive and fatal neurodegenerative disease that affects nerve cells in the brain and the spinal cord.
A person who works to increase awareness of and allocation of resources to ALS research, treatment, and/or other aspects of care.
The most common form of dementia, Alzheimer's is a degenerative brain disease involving the parts of the brain that control thought, memory, and language. Progression of Alzheimer's leads to mental deterioration, disorientation, memory disturbance, and confusion.
A laboratory test to detect and/or measure the amount or activity of a specific substance.
The evaluation of a test method (assay) to determine its fitness for a particular use.
Diseases in which the body's immune system attacks certain parts of the body "thinking" its own cells are foreign. Examples include multiple sclerosis, psoriasis, lupus. People with ALS are prone to developing autoimmune diseases.
Temporary paralysis of facial muscles that causes one side of the face to droop. Occurs after a condition (usually a virus) causes inflammation and swelling of the nerve that controls facial muscles. Most people with Bell's palsy recover without treatment.
A substance, biological structure, or biological process that can be measured in the body that informs and/or predicts the incidence and/or outcome of disease. It may also inform on whether a therapy is working. Three types of biomarkers: diagnostic, prognostic, and pharmacodynamic. Current ALS research–including that funded by Target ALS–is focused on biomarker discovery.
Quicker or above-average responses to tendon reflex tests.
bulbar onset ALS
ALS cases in which the initial symptoms involve difficulty in speaking or swallowing.
Mutations in this gene have been linked to ALS and frontotemporal dementia. C9orf72 mutations account for 25% to 40% of familial ALS cases and about 7% of sporadic cases
cALS (Caregiver of a Person with ALS)
A term in the ALS community that refers to caregivers for people with ALS.
central nervous system (CNS)
Composed of the brain and spinal cord, the CNS governs the majority of the body and cerebral functions
cerebrospinal fluid collection
Commonly called a spinal tap, this procedure extracts the fluid that surrounds the brain and spinal cord.
Also termed as "typical" ALS, it is characterized by a clinical presentation that is most common to the majority of ALS cases, it affects more than two-thirds of people with ALS and is usually fatal within four years of onset.
A bundle of nerves responsible for facilitating muscle control. They span from the brain cortex to the spinal cord.
A general term for the loss of loss of cognitive functioning–the ability to remember, think or make decisions.
A diagnostic biomarker detects or confirms the presence of a disease or condition, or identifies an individual with a subtype of the disease.
A term used in drug discovery to describe the likelihood that a drug will be able to adjust a biological target (such as a protein).
Weakness of the muscles used for speaking. Can cause slurred or slow speech, making it difficult to communicate with others.
The inability to swallow.
A long, enduring spasm within a particular muscle group.
Testing that evaluates and diagnoses disorders of the muscles and motor neurons by recording electrical activity and muscle response. Examples include electromyography and nerve conduction velocity.
Testing that records electrical activity of muscle tissue using electrodes attached to the skin or inserted into the muscle.
extrapyramidal system (EPS)
The part of the motor system involved in modulation and regulation of movement–for example, balance and walking.
A genetically inherited form of ALS that accounts for about 5% to 10% of all ALS cases.
frontotemporal dementia (FTD)
A progressive brain disorder that affects personality, behavior and language. Some people with ALS caused by C9orf72 gene mutations develop FTD
A field of study focused on understanding the activity of genes and other parts of the genome, including how they are regulated and the consequences of variation/mutation.
The process of introducing foreign genetic material (such as DNA or RNA) into cells using genetically engineered vectors.
The process by which the information from a gene is used to produce end products (such as proteins or other molecules).
gene mutation/mutated genes
A change in the DNA sequence that makes up a gene. Mutations are often caused by random errors during cell division and are often inheritable. They can also be caused by exposure to DNA-damaging agents such as radiation
The genetic makeup of an organism; in other words, it describes an organism's complete set of genes
glial derived neurotrophic factor (GDNF)
A naturally occurring substance that protects and contributes to the survival of motor neurons.
human-induced pluripotent stem cell (hiPSC or iPSC) line
Pluripotent stem cells self-renew and can produce any cell or tissue the body needs. Human-induced pluripotent stem cells are generated directly from adult cells. These cell lines can be used to test or identify new therapies in a lab
hybridoma and hybridoma clones
A hybridoma is a hybrid cell formed by the fusion of two different types of cells–typically, a short-lived plasma cell capable of producing antibodies and an immortal cancer cell. The hybridoma produces continuous supply (clones) of a specific monoclonal antibody. These clones are tested to identify the ones that produce the desired antibody
Hybridoma technology is a method for producing large numbers of identical antibodies (monoclonal antibodies).
When muscle tendons respond in an exaggerated manner to a normal stimulus.
A weak or nonexistent muscle tendon response to normal stimuli.
The study of the immune system, a set of processes that govern the body response to infections.
The inhibition of the body's immune system and its ability to fight infections and disease. May be intentionally caused to prevent rejection after transplant surgery. Other times, it is the result of diseases such as AIDS and lymphoma
Diseases that activate an abnormal response by the immune system in which it attacks the body's own tissues, resulting in inflammation.
A rare inherited neuromuscular disorder in men that causes progressive weakening of the muscles, especially the arms and legs. Also known as spinobulbar muscular atrophy. It is an example of a lower motor neuron disorder
limb onset ALS
When the initial ALS symptoms manifest as weakness in the limbs. Also called spinal onset ALS, it is the most common way ALS presents in a person.
lower motor neuron (LMN) disorders
A group of disorders that originate in the spinal cord, resulting in muscle atrophy and weakness.
lower motor neurons
Nerve cells that travel to the body's muscles, beginning in the spinal cord.
Information describing data. In genomic research, metadata includes where/how the DNA or RNA sequence was obtained, allowing researchers to reproduce or retrieve data more easily.
motor neuron disease
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
multiple sclerosis (MS)
An autoimmune disease affecting the central nervous system. MS involves the gradual destruction of myelin (the protective covering of nerves) throughout the brain and/or spinal cord. This interferes with nerve pathways, causing muscular weakness, loss of coordination and speech and visual disturbances.
Loss of muscle fiber volume that leads to a visible decrease in muscle size.
muscular dystrophy (MD)
A group of muscle diseases caused by progressive muscle degeneration and weakness due to the alterations of proteins involved in muscle health.
myasthenia gravis (MG)
A chronic autoimmune, neuromuscular disease that causes weakness and fatigue in the skeletal muscles, affecting the eyes, face, neck, and limbs. Its name means "grave muscular weakness."
nerve conduction velocity (NCV) tests
Also called a nerve conduction study (NCS), a test that measures how fast an electrical impulse moves through a nerve to assess nerve damage
An array of disorders that affect the brain cells and lead to progressive degeneration of the structure and function of the nervous system. Common neurodegenerative diseases include ALS, Alzheimer's disease and Parkinson's disease.
A group of disorders where the immune system mistakenly attacks parts of the central nervous system. These disorders include multiple sclerosis, neuromyelitis optica and transverse myelitis. ALS researchers are exploring the ways neuroimmune disorders interact.
The study of the interactions of the immune and nervous system.
The area of medicine that diagnoses diseases and treats disorders of the nervous system.
The regrowth or repair of any part of the nervous system.
The study of the nervous system and its disorders.
new candidate therapeutic targets
A recently identified gene, protein, or pathway that is associated with a disease, and treatments to modulate them may be beneficial to fight disease.
pALS (person with ALS)
A common term in the ALS community that refers to someone diagnosed with ALS.
Paralysis that is often accompanied by involuntary tremors.
A neurodegenerative disease caused by the loss of dopamine-producing brain cells resulting in difficulty controlling movement.
Although sometimes used interchangeably with pathology, pathobiology places greater emphasis on the biological aspects rather than the medical aspects.
The functional changes in the body associated with or resulting from disease or injury. It also refers to the study of such changes. It is a biological science, whereas pathology is a medical discipline.
A type of biomarker that helps to evaluate whether a treatment is working.
The study of drugs, their properties and effects.
An individual's observable traits (e.g., height, eye color, blood type).
Small circular pieces of DNA that can be replicated when inserted in cells. Plasmids can be delivered to cells in vectors in recombinant DNA research.
A dipeptide repeat protein (DPR) that accumulates in ALS as a result from mutations in the C9orf72 gene. DPRs have the potential to be used as biomarkers. Poly (GA) is the most abundant DPR in ALS and FTD patients with mutations in C9orf72, and contributes to TDP-43 abnormalities and neuron loss
A potential biomarker for ALS and FTD, poly (GP) is a dipeptide repeat protein (DPR) resulting from mutations in the C9orf72 gene. Increased levels of poly (GP) have been found in the spinal fluid of ALS and FTD patients with a C9orf72 mutation
A dipeptide repeat protein (DPR) that accumulates in ALS as a result from mutations in the C9orf72 gene. DPRs have the potential to be used as biomarkers. Poly (GR) may be the most toxic DPR to cells, and animal research suggests suppressing the production of Poly (GR) prevents its aggregation and ensuing neurodegeneration
primary lateral sclerosis
A motor neuron disease closely related to ALS. It affects only the upper motor neurons and progresses more slowly than ALS.
A type of biomarker that provides information on disease progression and/or outcome.
progressive bulbar palsy
A motor neuron disease that involves the brain stem—the bulb-shaped region containing lower motor neurons involved in swallowing, speaking, chewing and other functions. Initially, patients with progressive bulbar palsy only have muscle weakness that affects speech and swallowing. However, this condition often progresses to ALS
Proteins are the building blocks in all cells in all organisms. To produce them, DNA from genes is first transcribed into RNA, then RNA is translated into proteins.
A motor neuron disease closely related to ALS that primarily affects the ability to speak, swallow and chew. These symptoms resemble those of bulbar palsy, but this condition is also characterized by spontaneous or unmotivated crying and laughing
recombinant AAV (rAAV) production
The creation of adeno-associated viruses vectors that can infect cells but not damage them, for gene therapy.
A technique that can examine the quantity and sequences of RNA in a sample. It analyzes the transcriptome, which shows which genes encoded in DNA are turned on or off and to what extent
Abnormal hardening of body tissue.
speech-generating device (SGD)
Most commonly, a tablet-like device that allows a person to communicate through an electronic voice. Sometimes called augmentative communication equipment.
The type of ALS with no obvious family history. More than 90% of ALS cases are sporadic. The rest are familial.
Stress granules are structures that form within a cell due to stress conditions, including pathogen infection and other environmental stressors.
When separating fluids from solids, the supernatant is the liquid lying above the sedimented solids. Tissue culture supernatants can be a source of monoclonal antibodies. Examples include TALS 828.179 and TALS 828.66.
Also referred to as “gene modulation” or “target gene modulation,” it refers to the process of temporarily altering gene expression, including the silencing of a gene function or increasing expression. The goal of target modulation is to provide some benefit or conform for those suffering from specific ailments.
Process of demonstrating that a molecular target is directly involved in a disease process, and that modulation of the target will likely have a therapeutic effect. Validations involve performing tests several times to check the same outcomes are always obtained, or by performing tests by a different research group to support outcomes.
A protein typically found within the cell’s nucleus. In ALS patients, it becomes dysfunctional and clumps (aggregates). TDP-43 buildup occurs in about 97% of people with ALS — including those with and without genetic mutations. Ongoing research is focused on TDP-43’s potential as an ALS biomarker.
A gene (or genetic material) that has been isolated from one organism and then transferred into another.
upper motor neurons
Nerve cells that run through the spinal cord, starting in the brain's motor cortex.
whole genome sequencing (WGS)
A process that determines the complete DNA sequence of an organism's genome.