People with amyotrophic lateral sclerosis (ALS) have an altered fat composition in spinal cord cells. This has been confirmed by a pilot study carried out by researchers of the Biomedical Research Institute of Lleida (IRBLleida), the University of Lleida (UdL) and the Catalan Institute for Health. The study’s aim was to analyse the nuclear lipidome (the envelope of the cell site where genetic information is stored). The results, published in the Journal of Neurochemistry, support the usefulness of lipidomics applied to neurodegenerative diseases and the ageing process.
The pilot study has worked with samples from around 30 patients at the University Hospital Arnau de Vilanova (HUAV), the Santa Maria University Hospital (HUSM) and the Bellvitge University Hospital. ‘We have seen how the production of a special type of fat, called ether-lipids, could be altered in ALS patients,’ explains the researcher in charge and professor at the University of Lleida, Manel Portero. ‘We have observed a decrease in their concentration. We don't know if by solving this problem we can help patients, but it is a new potential avenue of action to discover new targets for the development of possible drugs,’ he adds.
The study has been led by Omar Ramírez-Núñez, Mariona Jové, Pascual Torres and Reinald Pamplona from the Metabolic Physiopathology group of the IRBLleida and the UdL’s Department of Experimental Medicine. It has been carried out in collaboration with the Catalan Institute for Health, the Foundation University Institute for Primary Health Care Research Jordi Gol i Gurina (IDIAPJGol- Primary Care Lleida), the Bellvitge Biomedical Research Institute (IDIBELL), The University of Barcelona and its Institute of Neurosciences (UBNeuro) and the Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED).
ALS is a neurodegenerative disease characterised by progressive loss of movement, as it affects motor neurons in the brain, brainstem and spinal cord, which are those responsible for transmitting the order for voluntary movement from the brain to the muscles. The causes of this minority disease are unknown. ‘We have proved that within ALS-affected tissues there are changes in lipids that could be related to the speed of the disease or even its cause. Further research is needed,’ says Portero.
Lipidomics is dedicated to the study and characterisation of lipids (fats), molecules that store energy in our body, form the envelopes of cells and play an important role in cell signalling. The lipidome or lipid profile of a cell indicates the composition and abundance of lipids in our organism. The IRBLleida and the University of Lleida have a scientific and technical lipidomics service, which has developed and consolidated the Lipidomics Platform of Catalonia (PLICAT).
The research has been possible thanks to the research grants received by the research staff: grant 278486 Seventh Framework Programme of the European Commission of the European Union; grant 2017SGR696 from the Agency for Management of University and Research Grants of the Catalan Government; grants PI14/1115, 14/003218 and PI17-00134 from the Carlos III Health Institute; grant RTI2018-099200-B-I00 from the Ministry of Science and Innovation; grant PP00111 from the Fundació la Marató of TV3, grant Marie Curie Cofund IRBLleida-IPP; grant FPU16/01446 from the Ministry of Education; grant FUNDELA, RedELA-Plataforma Investigación; and grant from the Miquel Valls Foundation.
Following the same line of research, a study published in the journal Brain Communications, led by Professor Manuel Portero-Otín and with the participation of the UdL researchers Joaquim Sol, Mariona Jové and Victòria Ayala, the Catalan Institute for Health, the IRBLleida and the IDIAPJGol and other researchers from the Bellvitge University Hospital, the IDIBELL, the University of Oxford, the King’s College London, the University of of Barcelona and the Columbia University, proves that the lipidomic characteristics of plasma and cerebrospinal fluid in people with ALS have a correlation with disease’s progression.
‘With some lipids, the higher their concentration in the cerebrospinal fluid, the faster the disease goes,’ explains Manel Portero. This finding will allow using lipid profiles as classifiers of ALS. In this case, the research has also been possible thanks to the research grants received by the research staff, which besides those mentioned above, also include the ERDF co-funding “A way tone build Europe” from the European Union.
Thanks to the PLICAT project, thousands of different lipid molecules from any biological system can be analysed, which facilitates the understanding of the role of lipids in health and human pathology, and can play a key role in the development of personalised medicine. Furthermore, the creation of this platform positions Lleida as a Catalan reference point in lipidomics, allowing new national and international collaborations to be established. The ERDF contributes 50% of the cost of the PLICAT, which is €625,000. The participating administrations and IRBLleida contribute the remaining 50%: IRBLleida contributes 64% of it (€400,000), the UdL contributes 23.20% (€145,000), and Agrotecnio and the Aliança ICS-GSS contribute 6.40% (€40,000) each.
Reserach Article:
Ramírez-Nuñez O, Jové M, Torres P, Sol J, Fontdevila L, Romero-Guevara R, Andrés-Benito P, Ayala V, Rossi C, Boada J, Povedano M, Ferrer I, Pamplona R, Portero-Otin M. Nuclear lipidome is altered in amyotrophic lateral sclerosis: A pilot study. J Neurochem. 2021 Apr 27. doi: 10.1111/jnc.15373. Epub ahead of print. PMID: 33905537.
Reserach Article:
Sol J, Jové M, Povedano M, Sproviero W, Domínguez R, Piñol-Ripoll G, Romero-Guevara R, Hye A, Al-Chalabi A, Torres P, Andres-Benito P, Area-Gómez E, Pamplona R, Ferrer I, Ayala V, Portero-Otin M. Lipidomic traits of plasma and cerebrospinal fluid in ALS correlate with disease progression. 2021 Apr 27.