The UB participates in a project to identify new therapeutic targets for diseases of the central nervous system
A research team from the University of Barcelona (UB) is taking part in a consortium to develop new therapeutic targets for diseases of the central nervous system, such as neurodegenerative pathologies and glioblastoma. More specifically, the project focuses on an innovative strategy, melitherapy, which is based on molecules that act directly on cell membrane lipids.
The overall goal of this consortium is to identify and study lipid-regulated receptors as a natural ligand with high therapeutic value and translational potential, in order to pave the way for future treatments against deficiencies in neurogenesis, cognitive impairment in ageing and brain tumour formation,” explains Professor Eva Estébanez, from the Department of Biochemistry and Molecular Biomedicine of the Faculty of Biology and the Institute of Biomedicine of the University of Barcelona (IBUB), who leads the University’s part in the project.
The consortium is led by Laminar Pharmaceuticals, a pioneer in the use of bioactive lipids through melitherapy. Researchers from the University of the Balearic Islands and the Biomedical Research Centre of La Rioja are also involved.
The potential of lipid-based molecules
In recent years, knowledge of the role of lipids in biochemical and physiological processes associated with different diseases has steadily expanded from considering them as mere structural molecules to becoming entities that regulate extremely important processes in the cell, and are an active part of them. This is the basis of melitherapy, a therapeutic approach that uses synthetic fatty acids that modify the composition of the cell membrane to interfere with the activity of membrane-associated proteins (responsible for various pathological processes), but also of key nuclear receptors that act as transcription factors.
In this context, the consortium’s researchers will try to identify and validate receptors capable of binding to lipid molecules; specifically, the designer lipids in Laminar’s portfolio, which are mostly synthetic fatty acids modified with respect to their natural counterparts, making them molecules with high efficacy and a high safety profile. Some of these molecules are already in advanced clinical phases (II and III), but many others are still awaiting development after having been tested only in a basic way and having shown some activity of interest.
“The methodology designed for the execution of the project maximises the options of finding targets of therapeutic interest, as it starts with those receptors and ligands that have already been studied most thoroughly and with which there is a high probability of success, but it also proposes a whole process of screening and selection of both targets and ligands that guarantee a thorough and exhaustive scrutiny, and which can therefore help to generate new patents and initiate new developments,” says Estébanez.
TLX, a receptor linked to a number of pathologies
In this sense, the project will focus mainly on the nuclear receptor (NR) superfamily as targets of great interest, since it is estimated that 25% of all drugs work through these receptors. In particular, the starting point is the receptor known as TLX (human tailless or NR2E1), which is crucial for understanding both the process of neurogenesis – the birth of new neurons – in the adult brain and for developing therapies against neurodegenerative diseases or oncogenesis in the central nervous system.
“The significance of TLX for various pathologies lies in its role in cell proliferation in the central nervous system, whose uncontrolled activation is oncogenic. However, controlled activation could be very important in neuroregeneration and for enhancing memory,” explains Estébanez, whose group has studied the structure and function of this receptor in depth.
In addition, TLX has oleic acid as a natural ligand, making it an ideal candidate to be modulated by one of the lipid molecules developed by Laminar. “Oleic acid is a metabolic regulator of TLX activity that can be used to selectively modulate the neural stem cells responsible for neurogenesis, paving the way for future therapeutic interventions to counteract deficiencies in this process,” she adds.
Impact on neurogenesis and cancer cell migration
Once receptors capable of binding to molecules in Laminar’s library have been identified, the consortium’s researchers will study the pathophysiological implications of the modulation of these receptors in cell and animal models in the two main areas of study addressed by the project: neurogenesis and the ability to inhibit cancer cell migration.
“The results of these studies will be the basis for the development of molecules capable of binding these receptors as drugs, which will expand the company’s pipeline and generate new treatment opportunities for pathological areas with great therapeutic needs. In addition, another objective is the validation of these identified therapeutic targets as biomarkers of neurodegeneration or treatment monitoring,” concludes Estébanez.
The project, reference SCPP2200C009586, is three years long and has obtained funding of 723,893.72 euros, of which 122,398 euros have been awarded to the UB within the framework of the 2022 call for public-private collaboration projects of the 2021-2023 Spanish National Plan for Scientific, Technical and Innovation Research, as part of the Recovery, Transformation and Resilience Plan.