Products
Therapeutic proteins are usually administered in the form of injection and infusion preparations and must be stored in a refrigerator. The first recombinant protein to be approved was human insulin in 1982. Some proteins, for example, are also available in tablet, capsule, and powder form and can be stored at room temperature, such as lactase for the treatment of lactose intolerance and other digestive enzymes.
Structure and properties
Proteins are macromolecules with a high molecular mass, composed mainly of amino acids. They are formed exclusively by living organisms in nature and are one of the basic components of all life on Earth (biomolecules). Natural proteins consist of the 22 different amino acids, each of which contains both an amino group and a carboxylic acid in the molecule. Each amino acid can bond with two others via peptide bonds (amides, -CO-NH-). Long chains are formed. Such a sequence is called a sequence. The chains arrange into a three-dimensional shape. Shorter chains with less than 50 amino acids are called peptides. Proteins belong to the group of biologics. They were initially isolated as drugs from natural sources such as organs. Since the development of recombinant DNA technology in the 1970s, they can be produced using biotechnological methods. Today, artificial or modified proteins with altered pharmacological and pharmacokinetic properties can also be produced. Genetically modified bacteria, fungi, and cells of animal or human origin, among others, are used for the production. Other structural elements such as polyethylene glycols (PEG) are also inserted in the process. Many proteins contain sugar residues. Glycosylation occurs only after translation in the Golgi apparatus and endoplasmic reticulum and may be required for therapeutic activity. It should be noted that proteins from bacterial expression systems such as are not glycosylated.
Effects
An important classical application of therapeutic proteins is substitution therapy. The drugs are added to the body to compensate for the insufficient formation or absence of a natural protein. Monoclonal antibodies are characterized by specific and high-affinity binding to a molecular target. A common mechanism of action is inactivation of the drug target. Antibodies can also induce signal transduction or cell destruction. Enzymes are biocatalysts that facilitate the breakdown or degradation of substances. Vaccines are components of pathogens that elicit an immune response and lead to immunity against infectious diseases. False receptors, for example, bind endogenous or foreign substances, inhibiting their effects.
Areas of application
Therapeutic proteins are widely used in medicine for diagnostic, prophylactic, and therapeutic purposes, and new drugs based on them are approved every year. Indications include, for example, asthma, atopic dermatitis, migraine, cancer, multiple sclerosis, osteoporosis, metabolic diseases such as diabetes, hyperlipidemia, and gout, hereditary diseases, hemophilia, and infectious diseases, to name just a small selection.
Active ingredients
Examples:
- Monoclonal antibodies such as adalimumab and trastuzumab.
- Enzymes such as lactase and rasburicase
- Receptors and fusion proteins such as abatacept and etanercept.
- Vaccines such as the flu shot
- Blood clotting factors such as factor VIII or factor IX
- Hormones such as insulins, somatropin, gonadotropins.
- Cytokines, interferons
- Toxins: Botulinum toxin
- Allergens
Dosage
According to the product information. Therapeutic proteins are most often injected parenterally as an injection or infusion because they are degraded in the digestive tract and therefore are not suitable for peroral administration. However, research is being conducted on orally available proteins, and inhalable insulin is commercially available. Proteins often have a long half-life and a correspondingly long dosing interval. For proteins with a short duration of action, an extension can be achieved by structural modifications such as pegylation. Rarely, therapeutic proteins can also be taken perorally – for example, digestive enzymes.
Abuse
Like other agents, some therapeutic proteins can be misused, such as recombinant erythropoietin (EPO) as a doping agent in sports.
Contraindications
Full precautions can be found in the drug labeling for each product.
Interactions
Proteins generally have a comparatively low interaction potential. It is also advantageous that they are endogenous products and no toxic metabolites are formed during degradation.
Adverse effects
Protein administration can lead to the development of autoantibodies directed against the therapeutic agents, reversing their effect. Immunogenicity may cause allergic reactions up to and including anaphylaxis. Proteins are very sensitive to environmental influences and due to the complex manufacturing process they are usually expensive products. Biosimilars, or copycat products of biologics, are somewhat less expensive.
