Search for specific drugs for inflammation

Álvarez Busca, Lucía

Elhuyar Zientziaren Komunikazioa

Anti-inflammatory drugs affect cells that intervene in inflammatory processes, but also those that are outside of this process. For this reason, it is important to develop specific anti-inflammatory drugs to prevent the involvement of cells without problems. A team of researchers from the UPV-EHU works with analogues of the C1P molecule with this objective.
Search for specific drugs for inflammation
01/11/2008 | Álvarez Busca, Lucía | Elhuyar Zientzia Komunikazioa

(Photo: Morguefile)
There are currently two main types of anti-inflammatory drugs: steroids and so-called NSAID (Non-steroidal anti-inflammatory drugs). The latter are used more often, with fewer side effects than the first, but with a broad spectrum. Therefore, there are no specific drugs to combat the inflammatory processes of each type of cell.

Under the direction of Antonio Gómez-Muñoz, the team works on the research of alternatives to these drugs creating analogs of the phosphate molecule C1P --cerida 1 phosphate. This molecule was first discovered in 1990 in a case of human leukemia. After his synthesis in the laboratory, they saw that he is an important mitogenic agent, which causes cell growth and blocks his natural death. After the study of the molecule, it has been observed that the inflammatory process tends to be affected, that is, when the cells detect this molecule release the molecules that produce inflammation, such as prostaglandins and cytokines.

But this does not happen with all kinds of cells. Although it seems contradictory, the same molecule produces an anti-inflammatory effect in several cell types. Hence this research group has departed: The elimination of the ability to cause inflammatory processes in the C1P molecule would allow its use as anti-inflammatory in certain types of cells without affecting the rest of the cells.

Remove one of the capacities

To do this, they have created synthetic molecules with a structure very similar to that of the C1P molecule, in collaboration with another research group in Barcelona. This group, led by doctors Josefina Casas of the IBMB-CSIC of Barcelona and Gemma Fabriás of the IIQAB-CSIC, is formed by Dr. Antonio Delgado of the University of Barcelona. They are pharmaceutical and organic chemicals that get the UPV team customized molecules.

So far they have tested 50 C1P analogues to measure. Three of them have achieved the result provided by the group, that is, they function as anti-inflammatory without causing inflammatory processes in other cells. These analogues do not generate prostaglandins, as does the C1P molecule, so there is no inflammatory process.

Computer monitor the reaction of drugs in cells.
L. L. Álvarez Álvarez
These three analogues have been tested with smooth muscle cells, macrophages and lung cancer cells obtaining the best results with the last two. This type of cells have been selected for their strong response to the molecules that cause inflammatory processes.

Inflammation and cancer

Inflammatory processes can have different origins, such as an infection. There are chronic inflammatory diseases that, due to their cellular instability, provoke in many cases processes of neoplasia - that is, the formation of new tissues of tumoral character -. This type of disease is ulcerative colitis and multiple sclerosis. This is because the state of continuous inflammation has a significant influence on cells. This can destabilize cells and cause uncontrolled growth of cells, as well as block the programming of cells to kill them by themselves.

At present there are very few groups that study the anti-inflammatory capacities of the molecule of C1P --in Virginia (USA), in the pharmaceutical company Novartis (Austria) and in certain research groups-, being the group of Antonio Gómez-Muñoz the first to study it in 1995. At the moment, the research has been tested at the cellular level, that is, it is in the first phase of the investigation. From now on they will have to test it in tissues and organs.

Summary: Summary:
The C1P molecule has two tendencies, depending on the type of cell that affects it: it can produce inflammation or be anti-inflammatory. In this research, the synthetic analogues of the molecule are being tested to eliminate its tendency towards the formation of inflammatory processes and to develop specific anti-inflammatory drugs, depending on the type of cell.
Director:
Antonio Gómez-Muñoz.
Working Team:
Patricia Gangoiti, Alberto Ouro, Lide Arana and María Granado.
Department:
Biochemistry and Molecular Biology.
Faculty: Faculty:
Science and Technology.
Financing: Financing:
MEC and the Basque Government.
Maria Granado, Lide Arana, Alberto Ouro, Antonio Gómez-Muñoz, Fabio Boliari (collaborator) and Patricia Gangoiti.
(Photo: L. L. Álvarez)
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