Teduglutide’s Discovery, Background, Gene Locus and Protein Structure
Teduglutide, chemically known as Gly2-glucagon-like peptide-2 (GLP-2), is a recombinantly derived analog of GLP-2, a naturally occurring hormone in the human body that regulates the growth and repair of the gastrointestinal lining. In the early 2000s, researchers at Novartis Pharma AG discovered this potential treatment for gastrointestinal disorders. Its gene locus has been traced to the GLP2R gene located on chromosome 17.
Structurally, Teduglutide is a 33-amino acid peptide composed of L-histidine, L-alanine, and L-glycine. It specifically mirrors the human GLP-2 protein structure except for a single amino acid substitution at the second position, where glycine replaces alanine, considerably enhancing its half-life.
Teduglutide Function
The primary function of Teduglutide is stimulating the growth of the intestinal lining, thereby improving nutrient absorption and gastrointestinal function. It binds to the GLP-2 receptor found on the protective intestinal cells known as enterocytes promoting the absorption and maintenance of nutrients and fluids.
Teduglutide-Related Signaling Pathways
Teduglutide primarily activates the GLP-2 receptor signaling pathway. Activation of this receptor triggers multiple intracellular pathways, most notably the PI3K-Akt-mTOR and MAPK pathways. These pathways play imperative roles in stem cell survival, proliferation, and differentiation of intestinal cells, ultimately enhancing the functionality and integrity of the intestinal lining.
Furthermore, Teduglutide lowers the apoptosis rate of enterocytes and increases their lifespan. Simultaneously, it reduces intestinal permeability and enhances the secretion of intestinal mucous, which is vital protective barrier against gastrointestinal pathogens.
Teduglutide Related Diseases
Teduglutide primarily addresses short bowel syndrome (SBS), a severe malabsorptive disorder normally following surgical removal of large sections of the small intestine. Consequently, patients with SBS are unable to absorb sufficient nutrients and fluids from their diet, leading to malnutrition and dehydration. Given its ability to promote the regrowth of the intestinal lining, Teduglutide is a game-changing solution in managing this otherwise challenging condition.
The Application of Teduglutide in Medicine
Teduglutide has presented an array of therapeutic benefits and holds broad promises in the medical field. Its approval by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treating SBS is a testament to its clinical effectiveness. Patients treated with Teduglutide have shown remarkable reductions in parenteral nutrition and intravenous fluid support, enhancing their quality of life significantly.
List of Drug Candidates Related to Teduglutide
Teduglutide itself is marketed under the brand name Gattex in the United States and Revestive in Europe. Other drug candidates primarily related to Teduglutide are glucagon-like peptides including Liraglutide (Victoza, Saxenda), Semaglutide (Ozempic, Rybelsus), Exenatide (Byetta, Bydureon), Dulaglutide (Trulicity), and Albiglutide (Tanzeum), which are being used for type 2 diabetes and weight management.
In summary, Teduglutide stands as a progressively influential medication specially designed to manage short bowel syndrome while showing potential applications in other gastrointestinal diseases. Its therapeutic journey from discovery to actual medical application is a vivid illustration of how in-depth scientific research can bring life-changing solutions into the sphere of medicine. With continuing research and development, the bounds of Teduglutide's applications might expand even further, offering hope in the treatment of other gastrointestinal conditions.
