Development and evaluation of a novel advanced lipoprotein test based on 2D Diffusion-ordered 1H NMR Spectroscopy

Roger Mallol Parera

Dr. Xavier Correig

Nutrition and metabolism

The objective of the doctoral thesis presented in this call was to develop a new methodology based on nuclear magnetic resonance (NMR) to determine other parameters of lipoprotein particles beyond their lipid content, such as the size and number of particles of various subclasses, as they have been shown to be better predictors of cardiovascular risk than cholesterol itself in high-risk patients. These individuals include patients with metabolic disorders, such as patients with obesity, diabetes and/or metabolic syndrome, among others. In order to achieve this objective, the doctoral thesis described in the attached document is the result of research carried out in the Department of Electronics, Electrical and Automation Engineering of the Universitat Rovira i Virgili (URV). Other research institutions have participated in this research, such as the Metabolomics Platform of the same university and the CIBER of Diabetes and Metabolic Diseases (CIBERDEM), and the Lipid and Arteriosclerosis Research Unit (URLA), also of the same university. All these groups are part of the Pere Virgili Health Research Institute (IISPV). Therefore, it is worth highlighting at this point the great collaborative and multidisciplinary aspect of this research, in which apart from the participation of different groups, researchers with such complementary profiles as engineers, physicists, chemists and doctors, among others, have also participated. Thanks to this collaboration, it has been possible to develop the LipoScale test, an advanced lipoprotein test based on diffusion NMR spectroscopy. This test is aimed at obtaining a better characterization of plasma lipoproteins, that is, lipid content, size and number of particles, in order to improve the prediction of cardiovascular risk. The main difference between our approach and the test that is currently only marketed in the USA is that in the latter case they use standard 1D NMR methods, while our test is based on the use of magnetic gradients, which generates 2D spectra with direct and objective information on the size of lipoprotein particles. This thesis has generated different scientific publications that are detailed in the attached document, as well as two patent applications that have been sent to the European Patent Office (EPO) and a spin-off. It is also worth noting that this work has also received a special mention in the form of 3rd Prize at the XXVII National Congress of the Spanish Society of Arteriosclerosis (SEA) last February 2014.

In order to carry out the industrial development phase of the in vitro diagnostic test developed within the framework of this doctoral thesis and, therefore, to be able to reach the final patient with guarantees, in December 2013 the spin-off Biosfer Teslab was created, founded by the entrepreneurial partners Núria Amigó and Roger Mallol, URV Professors Xavier Correig and Lluís Masana, and the two institutions involved in the same research, the URV and the IISPV. Work was carried out throughout 2013 to mature and validate the business idea, a process that generated a business plan that has been awarded by the URV Social Council for the Best Entrepreneurial Ideas, the 1st prize of the X ReusEmpresa Awards and the prize awarded by the International Young Chamber of Tarragona in Medical Innovation. Regarding the correct development of the company, we have received the support of different institutions and our advisors. In June 2013, Biosfer Teslab was selected to participate in the 6th edition of BioEmprendedorXXI, a business creation program in the field of life sciences organized by Barcelona Activa, Biocat and La Caixa Capital Risc. Later, in November 2013, it was also selected to participate in the VALORTEC course as finalists of the competition of the same name, VALORTEC organized by ACCIÓ. Regarding our advisors, apart from all the support we receive from our founding partners Xavier Correig and Lluís Masana, Biosfer Teslab is receiving external advice in different fields: regarding the correct development of the business through the IISPV, from the hand of its director, Dr. Oriol de Solà-Morales. External clinical advice is provided by Professor Alberico L. Catapano (President of the European Society of Arteriosclerosis, among other positions). On the other hand, Biosfer Teslab is advised in the commercial field by Baltasar Parra Monclús, a graduate in Medicine from the University of Barcelona (1992) and former Commercial Director of General Electric Healthcare. Finally, this summer Biosfer Teslab has achieved one of the most important milestones that it had planned in its development plan: closing a major financing round that would allow it to face with guarantees both the industrial development phase of the test and its subsequent commercialization. In this sense, this clinical and commercial interest in the test has resulted in the purchase of 30% of Biosfer Teslab by Laboratorios Rubió, a family business specialized in therapeutic solutions for low-prevalence diseases, to promote the development of this pioneering cardiovascular risk prediction test in Europe. Laboratorios Rubió will make an initial investment of approximately 300,000 euros to carry out the final phase of product development and its commercialization.

Nuclear Magnetic Resonance (NMR); Lipoprotein Particles; Lipid Content; Size; Number of Particles; Subclasses; Cardiovascular Risk; Cholesterol; High-Risk Patients; Metabolic Disorders; Obesity; Diabetes; Metabolic Syndrome; Doctoral Thesis; Department of Electronics, Electrical and Automation Engineering; Universitat Rovira i Virgili (URV); Metabolomics Platform; CIBER of Diabetes and Metabolic Diseases (CIBERDEM); Lipid and Arteriosclerosis Research Unit (URLA); Pere Virgili Health Research Institute (IISPV); Collaborative Research; Multidisciplinary Research; Engineers; Physicists; Chemists; Doctors; LipoScale Test; Diffusion NMR Spectroscopy; Plasma Lipoproteins; Prediction of Cardiovascular Risk; Magnetic Gradients; 2D Spectra; Scientific Publications; Patent Applications; European Patent Office (EPO); Spin-off; Special Mention; XXVII National Congress of the Spanish Society of Arteriosclerosis (SEA)