- Acute hemodynamic instability
The term “hemodynamic instability” is most commonly associated with an abnormal or unstable blood pressure, especially hypotension. More broadly, it is defined as global or regional perfusion that is not adequate to support normal organ function due to for example inefficient cardiac contraction.
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
An allergy is a specific type of immune reaction (type 1 hypersensitivity). The immune system may respond to foreign microorganisms or particles by producing specific proteins called antibodies. These antibodies are capable of binding to specific sites, or antigens, on the foreign particle. The recognition between antibody and antigen sets off a series of chemical and biological reactions designed to protect the body from infection. Sometimes, the body might overreact and produce antibodies against harmless, everyday substances such as pollen, dust, and animal dander. When this occurs, an allergy may develop against the offending substance (which is then called an allergen).
- Alzheimer's disease
A form of dementia, a progressive neurodegenerative disease that typically affects the elderly. Each patient may experience symptoms and disease progression very differently.
- American Thoracic Society (ATS)
The American Thoracic Society is a non-profit, international, professional and scientific society with a focus on respiratory disease, critical care and sleep medicine.
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.
- Aspartic proteinases
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".
- Autoimmune disease
An inappropriate response of the immune system against the body's own tissues.
- Autosomal recessive
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.
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.
- Biopharmaceutical company
A biopharmaceutical company uses biological techniques to produce a pharmaceutical product. Actelion is a biopharmaceutical company.
- Blood-brain barrier
- Bone crisis
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.
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.
- Cardiovascular disease
Any condition in which there is a disturbance in the function of the heart or blood vessels.
- Central nervous system (CNS)
The central nervous system compromises the brain and the spinal cord, and is the central control network for the entire body.
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.
- Chronic obstructive thromboembolic pulmonary hypertension (CTEPH)
Pulmonary hypertension associated with thrombotic or embolic diseases (Group IV according to the Venice classification).
- Circadian rhythm disorders
An innate cycle at approximately 24 hour intervals in the biochemical, physiological or behavioral processes of living beings, e.g., sleep/wake rhythm.
Irregular or pathological functioning of the circadian rhythm can result in disruption of one or more physiological processes at the cellular level, leading to conditions such as sleep disorders.
- Clinical Trial Application (CTA), EU
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.
- Clinical trials
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
- Community-acquired infections
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.
A group of proteins and peptides released by many types of cells which act as signaling molecules between cells.
- Diastolic pressure
The lowest level to which blood pressure falls between contractions of the ventricles, when the heart relaxes.
- Digital ulcers
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.
- Drug discovery
Research process to identify, select and optimize compounds (biological, genetic or protein targets linked to a particular disease) for clinical investigation.
- Drug resistance
A description of pathogens when they are unaffected by a drug or when the drug has a reduced effect on them.
Shortness of breath, difficulty breathing.
See also pulmonary arterial hypertension
Swelling resulting from fluid accumulation in tissue. When standing, edema occurs in the lower parts of the limbs.
- Eisenmenger's syndrome
Also called Eisenmenger's reaction. The process in which a left-to-right shunt in the heart causes increased flow through the pulmonary vasculature, causing pulmonary hypertension, which in turn causes increased pressures in the right side of the heart, and a reversal of the shunt into a right-to-left shunt.
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.
- Endothelin (ET)
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 receptor antagonist (ERA)
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 receptors (ETA and ETB)
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.
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)
Complex proteins (polymers of amino acids) produced by the living cell. As biochemical catalysts, they control chemical and metabolic reactions in living organisms.
- Enzyme replacement therapy (ERT)
A type of medical treatment for patients who lack an important enzyme, in which the missing enzyme is directly administered to the patient.
A process by which inflamed tissue becomes scarred in organs such as the lung, heart, or kidney.
See also idiopathic pulmonary fibrosis (IPF)
Standard medicinal preparations, containing one or more ingredients often in specifically defined concentrations, optimizing bioavailability of the drug.
- Gaucher cell
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.
- Genetic carrierA 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.
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
Carbohydrate-attached lipids which supply energy and serve as markers for cellular recognition.
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).
- 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.
- Heart failure
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.
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.
- Idiopathic pulmonary fibrosis (IPF)
A progressive and usually fatal disease, which may arise idiopathically (cause unknown), or in association with an underlying diseases such as systemic sclerosis. In IPF, fibrosis destroys both the structure and function of the respiratory system. Patients experience progressive dyspnea due to loss of lung function and scarring of the lung. As tissue becomes thicker it causes an irreversible loss of the tissue's ability to transfer oxygen into the bloodstream.
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.
Tissue death resulting from insufficient supply of oxygen, due to blockage of the blood supply to a localized area or organ.
- Investigational New Drug (IND), US
An application by a sponsor to the US Food and Drug Administration (FDA) for permission to conduct clinical investigations with a new drug.
- In vitro
A test or experiment carried out in an artificial environment such as a test tube.
- In vivo
A test or experiment carried out within a living organism.
- Ion channels
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.
- Lead compound
See white blood cells
- Lysosomal storage disorders
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).
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.
- Marketing Authorisation Application (MAA), EU
An application for marketing authorisation submitted by a pharmaceutical company within the European Union. In the EU a centralized procedure is available.
- Medicinal chemistry
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.
- Metabolic disorder
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.
- Molecular biology
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.)
- Myocardial infarctionAlso 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.
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.
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.
- New chemical entity (NCE)
A drug containing no previously-approved active ingredient.
- New Drug Application (NDA), US
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.
- Niemann Pick type C (NP-C) disease
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.
A scientific discipline involving the investigation of the molecular pathophysiology of cancer.
- Oral administration
Taking medication by mouth.
- Organic chemistry
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.
- Orphan disease
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.
- Orphan drug status
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.
See pulmonary arterial hypertension
- Patent application
An application to a patent office for a patent for an invention, which grants property rights to the inventor.
Viruses, bacteria or other microorganisms, proteins, or other agents that cause a disease.
A negative condition related to a disease or caused by a disease.
- Patient Information Leaflet (PIL)
A leaflet inserted in a drug package to inform the patient about the drug's approved indication and administration, and possible side effects.
- Peptide hormone
A hormone formed as a peptide, which is a linear molecule of one or more linked amino acids. They are secreted into the blood, have signaling functions, and interact with cellular receptors.
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.
- Phase I
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 II
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 III
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 IV
A cell that helps blood to clot; bruising and bleeding may occur more easily when the platelet count is low.
- Platform of expertise
Actelion's drug discovery core capabilities: enzymes, new chemical entities, ion channels, G-protein coupled receptors and anti-infectives.
- Portal hypertension
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.
- Preclinical studies / development
Studies required by drug development regulations to be conducted in animals to evaluate a candidate drug’s effects.
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 the cells of blood vessels. Prostacyclin is a member of the prostaglandin group of lipid molecules.
Prostacyclin exerts protective effects in the cardiovascular system, including vasodilatation and inhibits platelet aggregation and cell growth.
- Prostacyclin receptor agonist
A compound that selectively activates prostacyclin receptors (IP receptors). Effects include vasodilatation, and inhibition of platelet aggregation and cell growth.
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.
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)
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 artery
The vessel carrying blood from the heart to the lung.
- Pulmonary edema
Build-up of fluid in the lung, for example in the case of chronic heart failure.
- Quick eye movements
A neurological symptom in type 2 or type 3 Gaucher disease, characterized by quick, simultaneous movements of both eyes in the same direction.
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.
- S1P1 receptor agonist
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.
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.
- Secondary pulmonary arterial hypertension
Linked to the following complications or disease conditions: use of appetite suppressants, scleroderma, HIV/AIDS infection, and portal hypertension.
See also pulmonary arterial hypertension
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.
- SpleenThe organ that filters and stores blood and destroys abnormal red blood cells.
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.
- Substrate reduction therapy (SRT)
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.
- Summary of Product Characteristics (SmPC)
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.
- Supranuclear gaze palsy
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.
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.
- Type 1 Gaucher disease
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.
- Vascular smooth muscle cells
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.
Constriction or narrowing of the blood vessels that leads to, or aggravates, an increase of pressure in a given vessel.
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.
- Ventricles (heart ventricles)
The two lower or principal pumping chambers of the heart.
- White blood cells
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.
- WHO functional classification of PAH (WHO FC)
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