New therapeutic applications of retinoid-type compounds.
Spanish National Research Council (Consejo Superior de Investigaciones Cientificas, CSIC)
Retinoid-type compounds can modulate the uncoupling proteins (UCP) activity and increase or decrease the heat dissipation in cells. These compounds could be used in the treatment of obesity or cachexia present in cancer patients.
Pablo Zamorano Technology Transfer Expert, Technology Transfer Office Request more information
Mechanism of action
Retinoid-type compounds can be used to prepare a medicament being capable of in vivo modulating the uncoupling activity of UCP2.
SUMMARY A group of researchers has determined a new use for retinoid- type compounds. These compounds can modulate the uncoupling proteins (UCP) activity and increase or decrease the heat dissipation in cells. These compounds could be used in the treatment of obesity or cachexia present in cancer patients.
TECHNOLOGY DESCRIPTION Retinoids and, particularly retinoic acid, are known as natural molecules with important effects on cell differentiation. Retinoic acid (vitamin A acid) has found a very effective application in the treatment of severe forms of acne.
The new therapeutic applications considered for the retinoic acid point towards another field, i.e. that of disorders and diseases associated to the increase or decrease of the expression or the activity of uncoupling proteins.
Cellular respiration is a mechanism of oxidation of carbonated compounds which releases energy. It takes place in the mitochondria which are the organs responsible for cellular respiration. The so released energy is captured by the organism in diverse forms, particularly the synthesis of living matter, cell preservation, etc. If recovery of the energy is defective, oxidation continues but a major proportion of this energy is immediately dissipated as heat. Rupture of the link between respiration and energy recovery at mitochondria level is named uncoupling. The excessive production of heat can be regulated by two types of mechanisms: a) through the regulation of the genes encoded for certain proteins called uncoupling proteins or UCP proteins; or b) through a direct activation of the same proteins.
Various UCP proteins have already been identified as responsible for uncoupling respiration and thus for the dissipation of a portion of the energy as heat in mammals. This activity is of major relevance as UCP proteins can be considered therapeutic targets for the treatment of pathologies, disorders or diseases being associated to the regulation of energy consumption. Brown fat tissue, specialized in thermogenesis possess an uncoupling protein (UCP1). Another uncoupling protein, named UCP2, displays a high structural and functional homology with UCP1 but interestingly it is expressed in many human tissues, and its uncoupling activity is activated by retinoids. The fact that UCP2 is present in many human tissues, particularly in white adipose tissue, and that it has been demonstrated that UCP2 expression is increased in mice fed a high-fat diet and by leptin, seems to indicate that this protein could be a good target for the development of new anti-obesity compounds or for the treatment of cachexia in cancer patients. It is important to stress that obesity is a major problem in the majority of industrialized countries, in such a degree that obesity is frequently associated to serious pathologies as some type of diabetes or even to hypertension. The inventors describe in a patent application that it was possible to act on uncoupling proteins by using retinoid-type compounds. Thus, retinoid-type compounds can be used to prepare a medicament being capable of in vivo modulating the uncoupling activity of UCP2.
INNOVATIVE ASPECTS & COMPETITIVE ADVANTAGES The use of already know compounds for the treatment of new pathologies, which are designated as physiological disorders and diseases linked to the perturbation of the uncoupling activity of uncoupling proteins. Examples of these type of pathologies include among others, obesity or cachexia in cancer patients.
CURRENT STAGE OF DEVELOPMENT Development phase. The results obtained are performed in vitro. In vivo assays would be necessary to characterize the activity of the compounds.
European patent granted EP1018338. US patent pending US2002165280 and US2003229143.
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