Vascular Biology and Drug Development
The Laboratory of Vascular Biology and Drug Development has focused on the understanding of the molecular and cellular bases of atherosclerosis and other diseases in which chronic inflammation and low noise play a central pathogenic role (obesity, type II diabetes, neurodegenerative diseases , etc.).
In collaboration with other groups of our institute, we develop new strategies for the prevention and treatment of these diseases. The initial objective of the laboratory was to develop a new pharmacological strategy for the prevention and treatment of atherosclerosis, based on the design of a hybrid compound analogous to Vitamin E that possesses non-conventional anti-inflammatory properties.
Subsequently, we focus our research activities on the design and development of other non-conventional anti-inflammatory drugs that can be used for the treatment of other diseases in which chronic inflammation plays a central role (insulin resistance induced by obesity, hypertension). In this way, we have currently designed and developed four new families of non-conventional anti-inflammatory compounds that are patented in the US and internationally. We have recently licensed our portfolio of intellectual property and are committed to conducting clinical trials in humans (phase I / II) with our leading compound.
Development of a new pharmacological strategy for the treatment and prevention of atherosclerosis.
We designed a hybrid compound analogous to α-tocopherol to which we added a nitroalkenyl group. The rationale of our idea was that the nitroalkene analogous to tocopherol should be selectively incorporated into lipoprotein particles (particularly LDL) during its normal metabolism, due to the presence of chromanol in its structure and as does α-tocopherol. Once incorporated, LDL would act as carriers of our compound to the whole organism but including atherosclerotic damage, where the compound could exert the anti-inflammatory and anti-atherogenic properties of nitroalkenes. In order to test our hypothesis and test our compound in vivo, we developed different models of cardiovascular diseases in mice and demonstrated the efficacy of our compound for the prevention of atherosclerosis (J Rodríguez-Duarte et al., 2018; British Journal of Pharmacology).
Development of new pharmacological strategies for the prevention and treatment of diseases related to chronic inflammation.
After the development of our first generation of synthetic nitroalkenes, we focus our research activities on the design and development of non-conventional anti-inflammatory drugs for the prevention and treatment of different diseases in which chronic inflammation plays a central pathogenic role. We design and develop three new families of unconventional anti-inflammatory compounds that are protected in the USA. We licensed our portfolio of intellectual property and created a “Startup” (EOLO Pharma S.A.) to test our leading compound in clinical trials (phase I / II).
- Batthyány, C., Lopez, G. V., Dapueto, R., Escande, C. & Rodriguez-Duarte, J. Nitroalkene Trolox derivatives and methods of use thereof in the treatment and prevention of inflammation related conditions; WO/2018/037279 A1. USA, PCT patent (2018).
- Batthyány, C., Lopez, G. V., Escande, C., Porcal, W., Rodriguez-Duarte, J., Dapueto, R., Galliussi, G., Garat, M. P., Invernizzi, P., Ingold, M. & Collela, L. Nitroalkene Non-Steroidal Anti-Inflammatory Drugs (NA-NSAIDs) and Methods of Treating Inflammation Related Conditions; PCT/IB2017/058443. USA, PCT patent (2017).
- Batthyány, C., Lopez, G. V., Escande, C., Porcal, W., Dapueto, R., Rodriguez, J., Galliussi, G., Garat, M. P., Hill, M. & Segovia, M. Methods of treatment of inflammation related conditions using pluripotent anti-inflammatory and metabolic modulators; PCT/IB2017/056417. USA, PCT patent (2017).
- Batthyány, C. & López, G. V. Nitroalkene Tocopherol and Analogs for Use in the Treatment and Prevention of Inflammation Related Conditions; WO/2015/073527 A1. USA, PCT patent (2015).
- Batthyány, C. & Duran, R. Composition and Method for Inhibition of PknG from Mycobacterium Tuberculosis; WO/2014/204872. USA, PCT patent (2014).
2017-2019 – “Development of Eolo Pharma S.A: perform a clinical trial with a non conventional anti-inflammatory & immunomodulator compound”. CITES-GSS, Argentine (US$ 629.000/2 years; together with Dr. C. Escande and V. López).
2015 – 2016 – “Process development and validation for the study and valuation of nutraceuticals: creation of the first Uruguayan company of the CRO type”. Proyecto Alianza, ANII, Uruguay (USD 302.000/2 years; together with Dr. C. Escande).
2014 – 2015 – “Anti-atherogenic effects in vivo and anti-inflammatory mechanisms of nitroalkene analogs of tocopherol: a new pharmacological tool”. I+D CSIC Project, Uruguay (US$ 25.000/2years).
2015 – “Development of the zebrafish model for the study of atherogenesis and metabolic diseases and ‘screening’ of new drugs and natural anti-inflammatory and anti-atherogenic products”. Manuel Pérez Fundation Project, Faculty of Medicine, Udelar, Uruguay (US$ 12.000/1year).
2013 – 2015 -“Developmenent of new anti-atherogenic drugs: Nitroalkene -Tocopherol and Analogs”. CABBIO tri-nations Grant, Argentine, Brazil & Uruguay (US$ 35.000/2year).
- Rodriguez-Duarte J, Dapueto R, Galliusi G, Turell L, Kamaid A, Khoo NK, Schopfer FJ, Freeman BA, Escande C, Batthyany C*, Ferrer-Sueta G*, Lopez GV*. Electrophilic nitroalkene-tocopherol analogues: Synthesis, physicochemical and in vivo biological characterization of a novel class of non-conventional anti-inflammatory compounds. Scientific Reports (accepted with minor revisions). 2018 * co-correspopnding authors
- Rodriguez-Duarte J, Dapueto R, Galliusi G, Rossello J, Malacrida L, Kamaid A, Schopfer FJ, Escande C*, Lopez GV*, Batthyany C*. A novel nitroalkene-alpha-tocopherol analogue inhibits inflammation and ameliorates atherosclerosis in apoe knockout mice. British Journal of Pharmacology (submitted). 2018 * co-correspopnding authors
- Ingold M, Dapueto R, Victoria S, Galliusi G, Batthyany C, Bollati-Fogolin M, Tejedor D, Garcia-Tellado F, Padron JM, Porcal W, Lopez GV. A green multicomponent synthesis of tocopherol analogues with antiproliferative activities. European journal of medicinal chemistry. 2018;143:1888-1902
- Silva ARF, Lima DB, Leyva A, Duran R, Batthyany C, Aquino PF, Leal JC, Rodriguez JE, Domont GB, Santos MDM, Chamot-Rooke J, Barbosa VC, Carvalho PC. Diagnoprot: A tool for discovery of new molecules by mass spectrometry. Bioinformatics. 2017;33:1883-1885
- Muller V, Bonacci G, Batthyany C, Ame MV, Carrari F, Gieco J, Asis R. Peanut seed cultivars with contrasting resistance to aspergillus parasiticus colonization display differential temporal response of protease inhibitors. Phytopathology. 2017;107:474-482
- Folle AM, Kitano ES, Lima A, Gil M, Cucher M, Mourglia-Ettlin G, Iwai LK, Rosenzvit M, Batthyany C, Ferreira AM. Characterisation of antigen b protein species present in the hydatid cyst fluid of echinococcus canadensis g7 genotype. PLoS neglected tropical diseases. 2017;11:e0005250
- Batthyany C, Bartesaghi S, Mastrogiovanni M, Lima A, Demicheli V, Radi R. Tyrosine-nitrated proteins: Proteomic and bioanalytical aspects. Antioxidants & redox signaling. 2017;26:313-328