Compounds are chosen based on their potency, optimal dosage, and number of mutations that could benefit from therapy.
That Supreme Council for Scientific Investigations (CSIC) has signed an agreement with the American biopharmaceutical company Amicus Therapeutics and the University of Seville to participate in an international molecular research project called pharmacological companions applicable to the treatment of Fabry diseasea rare genetic condition that can affect the kidneys, heart and skin.
Pharmacological chaperones are small molecules that can bind to proteins that are unable to fold properly due to a genetic change, helping them to adopt their correct fold and thus restore their optimal function.
In proteins, the three-dimensional structure determines their function, so a point mutation that prevents it from folding properly and reaching its active form leads to a dysfunction that generally translates into severe pathologies. A pharmacological chaperone can specifically bind to the mutated protein, promoting its correct folding and restoring its function.
Origin of Fabry disease
The genetic mutations that cause Fabry disease disrupt the activity of an enzyme (lysosomal alpha-galactosidase) that processes biomolecules known as glycosphingolipids. As a result, these lipid substances accumulate in the walls of blood vessels in Fabry patients and adversely affect the functioning of various organs.
“The main problem in developing effective pharmacological chaperones is that after the molecule has bound to the mutated enzyme and assumed its final structure, it must be separated from it so that it can process the substrate, the accumulation of which causes the disease.” In this project we are pursuing different strategies to achieve this,” states the CSIC researcher Jose Manuel Garciafrom the Institute of Chemical Research (CIC Cartuja), which leads CSIC’s collaboration on the project.
The biopharmaceutical company Amicus Therapeutics has the only drug currently on the market that is based on the pharmacological concept of chaperone. This international project aims to develop new candidates second generation with activity and pharmacokinetic properties (related to assimilation, biodistribution and metabolism) improved. Compounds are chosen based on their potency, optimal dosage, and number of mutations that could benefit from therapy.
Although it may contain statements, data or notes from healthcare institutions or professionals, the information contained in Medical Writing is edited and edited by journalists. We encourage the reader to consult a doctor with any health-related questions.