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Development of a new family of compounds with potent anti-diabetic properties

Scientific
14 Mar 07

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Researchers have transferred the patent to the biotech enterprise Genmedica Therapeutics.

Researchers in the Molecular Medicine, and Chemistry and Molecular Pharmacology Programmes at the Institute for Research in Biomedicine (IRB Barcelona), together with scientists with the Organic Chemistry Platform of the Barcelona Science Park (Parc Científic de Barcelona, PCB), have identified a new set of compounds that show potent anti-diabetic properties that might provide a treatment for diabetes. The researchers have transferred the patent license to the biotech enterprise Genmedica Therapeutics, which will carry out the subsequent stages of the study on these new compounds.

In an article published recently in Diabetes –the journal with the highest impact in this field -, these researchers demonstrate that administration of these new molecules, either by subcutaneous injection or orally, to hyperglycaemic rats (high concentrations of glucose in blood) decreases the level of this polysaccharide to concentrations close to those shown by non-diabetic animals. Antonio Zorzano, head of the Molecular Medicine Programme at IRB Barcelona explains that “the most important finding has been the observation that these compounds exert a potent anti-diabetic effect in diabetic rats that produce almost no insulin. This opens up the possibility to develop a pill for the treatment of type I diabetes”. Affecting 10% of the population, diabetes type I is characterised by the incapacity of the body to produce insulin (the hormone made in the pancreas that regulates blood sugar levels), and to date can be treated only with injections of this hormone.

The director of the PCB and principal investigator of the Combinatorial Chemistry Group at IRB Barcelona, Fernando Albericio, has worked alongside Miriam Royo, manager of the PCB’s Combinatorial Chemistry Platform, to design and synthesise the compounds, which are vanadium salts and arylalkylamines. “The presence of amine and vanadate in the same chemical entity has allowed us to slightly decrease the concentration of the latter, thereby reaching very low levels. These characteristics make these compounds of interest as potential drugs”, comments Miriam Royo.

Fernando Albericio: "The patent for these compounds has been rapidly transferred to a technology-based enterprise in order to continue the cycle through which research results are transferred back to society through improvements in quality of life”.

These compounds may also be of use for the treatment of several monogenic diseases, such as type A insulin resistance syndrome, for which no treatment is currently available. This kind of disease is characterised by failure of cell insulin receptors. By examining the signalling pathways, these researchers have shown that the compounds activate the cell process. “This finding allows us to hypothesise that these compounds act as bypasses when the cell mechanisms that trigger insulin receptors fail”, explains Zorzano.

The study on the biological properties of this new family of compounds has also provided a new finding of interest. These compounds were also observed to decrease lipid concentrations in blood, such as cholesterol and triglycerides, the metabolic alteration of which leads to a risk of developing cardiovascular diseases.

The collaboration between two of the programmes run by IRB Barcelona has been crucial for the development of this project. For Antonio Zorzano, molecular biologist specialised in the study of diabetes, “working side by side the organic chemists at the same institute and at the PCB for three years has greatly benefited the research; without this collaboration it would have been much more difficult to carry out this project”. This study has also involved scientists from the University of Salamanca, the Institut National de la Santé et de la Recherche Médicale de Toulouse (INSERM U586), and the Sant Joan de Déu Hospital (Barcelona).

In the words of Fernando Albericio, “it is an excellent example of new synergies that are developed in the PCB. Two research groups belonging to distinct disciplines, collaborating with a Technology Platform, have produced a set of compounds with potential therapeutic properties. The patent for these compounds has been rapidly transferred to a technology-based enterprise in order to continue the cycle through which research results are transferred back to society through improvements in quality of life”.

Source article:
Oral insulin-mimetic compounds that act independently of insulin
Garcia-Vicente S., Yraola F., Marti L., González-Muñoz E., García-Barrado M.J., Canto C., Abella A., Bour S., Artuch R., Sierra C., Brandi N., Carpene C., Moratinos J., Camps M., Palacín M., Testar X., Guma A., Albericio F., Royo M., Mian A., Zorzano A.
Diabetes 56(2):486-93. (Feb 2007)

About IRB Barcelona

Created in 2005 by the Generalitat de Catalunya (Government of Catalonia) and University of Barcelona, IRB Barcelona is a Severo Ochoa Centre of Excellence, a seal that was awarded in 2011. The institute is devoted to conducting research of excellence in biomedicine and to transferring results to clinical practice, thus improving people’s quality of life, while simultaneously promoting the training of outstanding researchers, technology transfer, and public communication of science. Its 28 laboratories and eight core facilities address basic questions in biology and are orientated to diseases such as cancer, metastasis, Alzheimer’s, diabetes, and rare conditions. IRB Barcelona is an international centre that hosts 400 employees and more than 30 nationalities. It is located in the Barcelona Science Park. IRB Barcelona is a CERCA center, and a member of the Barcelona Institute of Science and Technology (BIST).

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