A
B
C
D
E
F
G
H
I
L
M
N
O
P
Q
R
S
T
V
W
A

A compound, hormone or neurotransmitter imitating a substance found for example in or on human cells. By binding to a specific cell receptor, it can alter the receptor activity as if it were the specific substance itself.

See also antagonist

S1P1 receptor agonism
Prostacyclin receptor agonism

A pathological deficiency in the oxygen-carrying component of the blood, measured in concentrations of hemoglobin, red blood cell volume, or red blood cell number.

A substance that opposes or alleviates the pharmacological effect of another compound. By binding to specific cell receptors, an antagonist can oppose, lessen or block the activity of an agonist acting on the same cell receptors.

Endothelin receptor antagonism

Substances which reduce the growth of, or kill, the growth of microorganisms such as bacteria.

Infectious diseases

See antibiotics

A family of enzymes which cleave within proteins, and which achieve their activity by using an arrangement of two aspartic acids at their active site to activate a water molecule, which then acts as a chemical "scissor".

A procedure or test in which a property such as biological activity or cellular signaling is measured.

Drug discovery process

The American Thoracic Society is a non-profit, international, professional and scientific society with a focus on respiratory disease, critical care and sleep medicine.

An inappropriate response of the immune system against the body's own tissues.

Immunology

A pattern of inheritance in which both copies of an autosomal gene must be abnormal for a genetic condition or disease to occur.
If both parents have one abnormal copy of the same gene, the chance that their offspring will have the disorder is 25% for each pregnancy.

Genetic disorders
How is Gaucher disease diagnosed?
B

Describes the extent (usually as a percentage) to which an administered substance reaches the systemic circulation. If a medication is administered intravenously, all of it reaches the blood, so it is 100% bioavailable by definition. If the drug is taken orally, the bioavailability is lower because the drug's absorption is incomplete, and the concentration is reduced before it arrives in the circulatory system.

A scientific discipline involving the study of chemical substances, processes and reactions in living cells, tissues, organs and organisms.

A biopharmaceutical company uses biological techniques to produce a pharmaceutical product. Actelion is a biopharmaceutical company.

A layer of tightly-packed cells in and around the small blood vessels in the brain that prevent many medications and other substances from entering the brain. It serves to protect the central nervous system.

Central nervous system

Also called bone infarction, which means tissue death, in this case in the bones. Tissue dies because of a lack of oxygen as a result of a blocked blood supply.

C

A group of diseases in which cells grow unrestrained in an organ or tissue of the body. Uncontrolled cell growth can spread to tissues around it, and destroy them, or be transported through blood or lymph pathways to other parts of the body.

Oncology

Any condition in which there is a disturbance in the function of the heart or blood vessels.

Cardiovascular disorders

The central nervous system compromises the brain and the spinal cord, and is the central control network for the entire body.

Central nervous system

A chitinase enzyme found in the blood. Its enzymatic activity is markedly elevated in the serum of patients suffering from lysosomal lipid storage disorders such as Gaucher disease. Levels are significantly increased in patients with symptomatic Gaucher disease. Chitotriosidase can be used as an indicator of the severity of the disease.

Type 1 Gaucher disease

The submission of an application by a drug manufacturer to a regulatory authority of an EU Member State, requesting authorization to conduct a clinical trial with an investigational medicinal product.

Drug discovery & development

After a compound has undergone rigorous testing in drug discovery and preclinical development, its pharmacological and/ or other pharmacodynamic effects and its safety and efficacy are investigated in humans.

See also Phase I, Phase II, Phase III and Phase IV

Clinical trials

Infections acquired through daily interactions within a community, in contrast with hospital-acquired infections. Generally, the two types of infections differ in their response to medicines.

D

The lowest level to which blood pressure falls between contractions of the ventricles, when the heart relaxes.

Necrotic lesions located on the fingers, a common complication of systemic sclerosis.
Digital ulcers are very painful, and result in difficult-to-heal open sores on fingers and toes. They leave depressed scars and adversely impact the ability to perform work and daily activities, particularly those associated with fingertip functions. In severe cases, infection can become a complication, leading to osteomyelitis and gangrene, for which surgery and even amputation may be required.

Endothelin system

Research process to identify, select and optimize compounds (biological, genetic or protein targets linked to a particular disease) for clinical investigation.

Drug discovery process

The reduction in therapeutic benefit in a subject who has been exposed to a medicinal product continuously (e.g., due to the emergence of resistant virus in the treatment of HIV).

Infectious diseases strategy

Shortness of breath, difficulty breathing.

See also pulmonary arterial hypertension

E

Swelling resulting from fluid accumulation in tissue. When standing, edema occurs in the lower parts of the limbs.

A scientific discipline concerned with the study of electrical activity in biological cells and tissues. Electrophysiologists measure voltage change, or electrical current flow, on a wide variety of scales, from single ion channel proteins to whole tissues such as the heart.

A peptide hormone produced by the endothelium and known to be one of the most potent of the endogenous vasoconstrictor hormones. Recent research shows that ET is also a growth factor, a promoter of fibrosis and inflammation, and a key initiator of endothelial dysfunction. ET-1 is the predominant form, and is produced by endothelial cells.

Endothelin system

A substance that binds to receptors in place of endothelin, thereby hindering the effect of endothelin on the cell. As an approach for the treatment of endothelin-related disorders such as pulmonary arterial hypertension (PAH) ERAs work by reducing vascular resistance and potentially improving blood circulation (hemodynamics). This mechanism enables clinicians to both treat symptoms and stabilize the disease.

Endothelin receptor antagonism

Endothelin receptor A (ETA) and endothelin receptor B (ETB) are the docking places on a cell where endothelin binds. ETA and ETB receptors help to regulate the dilation and constriction of blood vessels throughout the human body. In addition, these two receptors located in the smooth muscle cells, fibroblasts, and endothelial cells, mediate cell proliferation, fibrosis and hypertrophy. In pulmonary arterial hypertension (PAH), the ETA and ETB receptors bind endothelin (ET-1) produced by endothelial cells. This leads to severe vasoconstriction, smooth-muscle-cell growth, and hypertrophy, seriously limiting blood flow through the lungs.

Endothelin receptor antagonism

The innermost cell layer in blood vessels separating the bloodstream from the vessel wall. The endothelium plays an important role in the maintenance of the integrity of blood vessels.

See also Endothelin (ET)

The endothelium

Complex proteins (polymers of amino acids) produced by the living cell. As biochemical catalysts, they control chemical and metabolic reactions in living organisms.

A type of medical treatment for patients who lack an important enzyme, in which the missing enzyme is directly administered to the patient.

How is GD1 diagnosed?
F

A process by which inflamed tissue becomes scarred in organs such as the lung, heart, or kidney.

See also idiopathic pulmonary fibrosis (IPF)

Endothelin system
G

Standard medicinal preparations, containing one or more ingredients often in specifically defined concentrations, optimizing bioavailability of the drug.

A macrophage that is enlarged from the build-up of glucosylceramide substrate. Gaucher cells are characteristic of Gaucher disease, and are found particularly in the spleen, liver and bone marrow, but also in other tissues such as the lungs, skin, eyes, kidney, heart, and, in some instances, the nervous system.

A genetic carrier (or simply 'carrier') is a person, or other organism, that has inherited a genetic trait or mutation, but does not display/manifest that trait or show symptoms of the disease. A carrier is, however, able to pass the gene to offspring, and the offspring may then express the gene.

An enzyme which is needed to break down glucosylceramide and which is deficient in type 1 Gaucher disease.

Type 1 Gaucher disease (GD1)

The fatty substrate that accumulates primarily in the macrophages of people with type 1 Gaucher disease to levels that can lead to various physiological effects such as enlarged liver and spleen.

See also Gaucher cell

Type 1 Gaucher Disease (GD1)

Carbohydrate-attached lipids which supply energy and serve as markers for cellular recognition.

Type 1 Gaucher disease (GD1)

G proteins can bind guanine nucleotides GDP and GTP. They are made of three different sub units associated with the inner surface of the plasma membrane and with transmembrane receptors called G protein coupled receptors (GPCRs).

When a hormone, or a ligand, binds to this receptor, the G-protein is activated and subsequently transmits biochemical signals across the cell membrane.

H

Occurs when the heart muscle loses its ability to pump enough blood to meet the body's metabolic needs. The condition falls under two categories: acute heart failure and chronic heart failure.

The forces generated by the heart and the motion of blood through the cardiovascular system.

Cardiovascular disorders

The iron-containing oxygen-transport protein in red blood cells, which transports oxygen from the lungs to the rest of the body.

Substances produced by a living cell. As hormones pass into the blood stream they are carried to their target organs and tissues, where they produce specific effects. Overall, they act to modify the structure or function of organs and tissues.

I

A scientific discipline involving the study of the immune system. Immunology focuses on the physiology and pathology of the immune system in immunological disorders such as autoimmune diseases, immune deficiency, hypersensitivity and allergies and transplant rejection.

Immunology
S1P system

A test or experiment carried out in an artificial environment such as a test tube.

A test or experiment carried out within a living organism.

Tissue death resulting from insufficient supply of oxygen, due to blockage of the blood supply to a localized area or organ.

An application by a sponsor to the US Food and Drug Administration (FDA) for permission to conduct clinical investigations with a new drug.

Transmembrane pores that allow the passage of ions (charged molecules) into or out of a cell. There are hundreds of different ion channels, distinguished by ion selectivity, opening mechanism, and protein sequence. Ion channels can be opened by chemical ligands, voltage fluctuations, acidity changes, temperature variations, or mechanical stimuli such as touch or sound.

L

A chemical that shows desirable efficacy and toxicological characteristics, and which may be considered for further development.

Drug discovery & development
Drug discovery process

See white blood cells

A class of genetic disorders, caused by the deficiency or malfunction of specific enzymes found in cell lysosomes, and which lead to the accumulation of waste material in cells.

A sac-like compartment inside cells in which enzymes break down waste molecules for reuse (recycling).

M

A specialized cell type with many different functions including the destruction of bacteria and foreign particles, production of chemokines, antigen processing and presentations, as well as degeneration of the body's own, worn out cells. The macrophages "eat" these cells, degrade them into smaller molecules inside cell compartments called lysosomes, and subsequently release these smaller molecules for re-use in new cells.

S1P1 agonism

An application for marketing authorisation submitted by a pharmaceutical company within the European Union. In the EU a centralized procedure is available.

Drug discovery & development

A scientific discipline between chemistry and pharmacology, which includes the design, synthesis and development of substances that eventually become pharmaceuticals. The study of existing drugs, their biological properties, and their quantitative structure-activity relationship (QSAR), is also a focus of medicinal chemistry.

The body derives energy from food by breaking down proteins, carbohydrates and fats into sugars and acids, a process called metabolism. A metabolic disorder is a medical condition that involves the disruption of the normal metabolism by abnormal chemical reactions, e.g., missing enzymes.

Type 1 Gaucher disease (GD1)

A scientific discipline involving the study of biology at a molecular level, focusing mainly on physiochemical and biological organization (interaction and regulations) and synthesis of cell systems. (Including ribonucleid acid (RNA), which is essential for protein synthesis in all living cells, deoxyribonucleid acid (DNA), which carries genetic information and proteins.)

Also called a heart attack. The death of heart muscle tissue (myocardial tissue) due to deprivation of circulating blood.

A brief uncontrolled twitching or contraction of a muscle or group of muscles.

N

The study of the anatomy, physiology and pathology of the nervous system, also at the nerve cell level. Neurobiology is concerned with how different nerve cells are organized together, and how they process information and ultimately mediate the behavior of the organism.

Affecting the brain or nervous system. Many lysosomal storage disorders have both neuronopathic and non-neuronopathic types.

Type 1 Gaucher disease (GD1)

A chemical sending nerve impulses from a neuron to another cell, which can set off a signal in the receiving cell, or stop the transmission of a signal. The signal is usually followed by a specific effect in the receiving cell.

Central nervous system

A drug containing no previously-approved active ingredient.

An application submitted by a drug sponsor to the US Food and Drug Administration (FDA) for approval of a new pharmaceutical for sale and marketing.

Drug discovery & development

A rare genetic disorder affecting mostly childhood and adolescence. It is life threatening with a short life expectancy. The underlying cause is a protein defect leading to impaired intracellular lipids trafficking. As a consequence, glycosphingolipids (GSL) accumulate in neurons, leading to neuronal cell dysfunctioning and death, and clinically to severe neurological manifestations.

A medical condition without neurological symptoms.

O

A scientific discipline involving the investigation of the molecular pathophysiology of cancer.

Oncology

Taking medication by mouth.

A scientific discipline involving the study of carbon compounds and their reactions. A wide variety of classes of substances – such as drugs, vitamins, plastics, natural and synthetic fibers, carbohydrates, proteins, and fats – consist of organic molecules.

A rare, life threatening disease affecting fewer than 200,000 persons in the United States / or fewer than 5 per 10,000 persons in the European Union.

A designation (also known as an orphan medicinal product) to provide incentives (tax reductions and marketing exclusivity for an extended time) for companies to develop and market treatments for orphan diseases.

P

See pulmonary arterial hypertension

An application to a patent office for a patent for an invention, which grants property rights to the inventor.

R&D approach

Viruses, bacteria or other microorganisms, proteins, or other agents that cause a disease.

Infectious diseases

A negative condition related to a disease or caused by a disease.

The biochemical and physiological effects of drugs on the body, the mechanisms of drug action, and the relationship between drug concentration and effect.

The effect of the body on a drug after administration – how a drug is absorbed, distributed, metabolized and eliminated.

A scientific discipline involving the study of the effects of drugs in a living organism, with the focus on the interaction and reaction of the drug in the body, mainly in regard to its therapeutic value.

Clinical studies which are the first stage of testing in human subjects, normally performed with a small group of healthy volunteers. This phase includes trials designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of a drug.

Phase I

Clinical studies performed with patients rather than healthy volunteers, early in the drug development process. While this phase continues to provide safety data as the number of people receiving the drug increases, the focus of these studies is the efficacy of the drug, proof of the hypothesis of how the drug works, and determining the appropriate dose/s for larger trials.

Phase II

Large clinical studies intended to be the definitive assessment of the drug under investigation, providing additional safety data, confirming efficacy, and providing comparative data where an approved therapy for the indication under investigation is already available.

Phase III
Clinical trials

Clinical studies conducted after a drug has received marketing approval, normally intended to collect data on long-term safety and efficacy for approved compounds, or to provide technical support for an approved therapy.

Phase IV
Clinical trials

A leaflet inserted in a drug package to inform the patient about the drug's approved indication and administration, and possible side effects.

A cell that helps blood to clot; bruising and bleeding may occur more easily when the platelet count is low.

Actelion's drug discovery core capabilities: enzymes, new chemical entities, ion channels, G-protein coupled receptors and anti-infectives.

Platform approach

An increase in blood pressure in the portal vein leading to the liver, caused either by a disease such as cirrhosis, or by blood vessel blockage.

Studies required by drug development regulations to be conducted in animals to evaluate a candidate drug’s effects.

Drug discovery process

An inactive substance that undergoes a metabolic process in the digestive tract and is thereby changed into an active drug. A prodrug is used when the active ingredient is too unstable to be used as a drug by itself.

A natural chemical produced by cells throughout the body. Prostaglandin exerts a broad range of physiological functions, including regulation of cardiovascular, reproductive, and inflammatory processes.

Prostacyclin system

A compound that selectively activates prostacyclin receptors (IP receptors). Effects include vasodilatation, and inhibition of platelet aggregation and cell growth.

Prostacyclin system

Enzymes in an organism, which break down proteins and peptides, through the hydrolysis of peptide bonds.
The term protease describes proteinases, which cleave peptide bonds within the peptide, as well as exo-peptidases, which take one or two residues off the ends of a peptide.

Enzymes cleaving peptide bonds within proteins – a subset of proteases.

Pulmonary arterial hypertension (PAH) is a life-threatening disease of the arteries connecting the lungs to the heart (the pulmonary arteries). As PAH develops, blood flow through the pulmonary arteries is restricted. The right side of the heart is put under increasing strain to pump blood through to the lungs, and this causes the right side of the heart to become enlarged. This process leads to the main symptoms of PAH – breathlessness, chest tightness, limited exercise capacity, and fatigue.

Pulmonary arterial hypertension (PAH)

The vessel carrying blood from the heart to the lung.

Build-up of fluid in the lung, for example in the case of chronic heart failure.

Q

A neurological symptom in type 2 or type 3 Gaucher disease, characterized by quick, simultaneous movements of both eyes in the same direction.

R

Research and development

Initiates signaling between and within cells, and has a molecular structure in which a ligand, such as a hormone, can bind. The binding of a ligand to the receptor initiates a change in cell function, which leads to a secondary event, such as cell signaling, vasoconstriction, or release of hormones.

S

In autoimmune diseases, cells of the immune system (lymphocytes) aberrantly attack the body’s own tissues, e.g. nerve cells or skin.
As a receptor agonist, S1P1 prevents the lymphocytes from moving into the lymphatic and vascular circulation and thus prevents the mis-reaction of the immune system.

S1P1 agonism

A chronic autoimmune disease of the connective tissues. Patients with scleroderma develop a blood vessel abnormality and degenerative changes in joints, skin, and other organs.

Linked to the following complications or disease conditions: use of appetite suppressants, scleroderma, HIV/AIDS infection, and portal hypertension.

See also pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH

The regulatory approved information about the composition, pharmaceutical form, clinical particulars, pharmacological properties, pharmaceutical particulars and details about the marketing authorization of a product in the European Union.

Also called muscular hypertonicity. A neurological symptom in type 2 or type 3 Gaucher disease. Spasticity is a disorder of the body motor system, and especially of the central nervous system (CNS), in which certain muscles are continuously contracted. This contraction causes stiffness or tightness of the muscles, and may interfere with gait, movement, and speech.

Type 1 Gaucher disease (GD1)

The organ that filters and stores blood and destroys abnormal red blood cells.

Type 1 Gaucher disease (GD1)

The substance on which an enzyme acts in a biochemical reaction. The enzyme binds to the substrate, forming an enzyme-substrate complex. After the substrate is broken down into a product, it is released from the enzyme.

An oral therapy for type 1 Gaucher disease, which reduces the amount of substrate made in the body. Hence, in conditions such as type 1 Gaucher disease, where the catabolism or enzymatic breakdown of the naturally-occurring substrate is impaired, there is less substrate for the defective enzyme to break down.

Type 1 Gaucher disease (GD1)

A neurological symptom in type 2 or type 3 Gaucher disease. It is an eye movement abnormality in which the two eyes move together but have limited movement in one direction.

Type 1 Gaucher disease (GD1)
T

A scientific discipline involving the study of adverse effects of substances on living organisms, including the effects of very high concentrations of substances, which, at normal concentrations, may have therapeutic benefits.

A genetic metabolic disorder in which a fatty substance accumulates in the body, especially in the spleen, liver, lungs, and bone marrow. The disorder is characterized by bruising, fatigue, anemia, low count of blood platelets, and enlargement of the liver and spleen.

Type 1 Gaucher disease (GD1)
V

The cells located mainly in the middle wall-layer (tunica media) of blood vessels, controlling the dilation and constriction of blood vessels. ETA and ETB receptors are present on these cells.

Prostacyclin system

Constriction or narrowing of the blood vessels that leads to, or aggravates, an increase of pressure in a given vessel.

Cardiovascular disorders

Sudden contraction of the muscular walls of the blood vessels, with a resultant reduction in blood flow. Vasospasm may rise as a consequence of aneurysmal subarachnoid hemorrhage.

Cardiovascular disorders

The two lower or principal pumping chambers of the heart.

W

Also called leukocytes. Cells of the immune system which defend the body against both infectious diseases and foreign materials.

The World Health Organization (WHO) is the United Nations agency focusing on worldwide and regional health issues.

The classification of patients with pulmonary arterial hypertension into one of four groups, depending on severity:

• Functional Class I – Patients without resulting limitation of physical activity
• Functional Class II – Patients with slight limitation of physical activity
• Functional Class III – Patients with a marked limitation of physical activity
• Functional Class IV – Patients with the inability to carry out any physical activity without symptoms

Pulmonary arterial hypertension (PAH)