VALENCIA, 27 Nov. (EUROPA PRESS) –
A multidisciplinary research team made up of several institutes of the Higher Scientific Research Council (CSIC), the Polytechnic University of Valencia (UPV), and other academic and clinical institutions has developed a new non-steroidal anti-inflammatory drug (NSAID) that can replace corticosteroids. .
This medication has fewer adverse effects and toxicity than corticosteroids and, unlike corticosteroids, preserves the innate immune system, as reported by the CSIC and the UPV in separate statements. This compound is capable of inhibiting the cytokine storm associated with severe inflammation while preserving innate immunity.
The substance, called AG5, is a synthetic derivative of a compound of plant origin that has already been tested in several animal models, proving its usefulness in inhibiting one of the most serious effects of inflammatory processes associated with infections such as Covid-19. cancer and other chronic inflammatory diseases.
The results, which include several patents, are published in Biomedicine and Pharmacotherapy. During the Covid-19 pandemic, clinical trials in hospitalized patients confirmed that corticosteroids such as dexamethasone reduced mortality, but were harmful when applied at the first symptoms of the infection, the CSIC and the UPV have noted.
Thus, they have explained that this is because the strong immunosuppressive activity of these drugs weakens the primary immune response, which causes a delay in the elimination of the infection and adverse results in severe viral pneumonia.
In this scenario, they added, in March 2020 the Higher Scientific Research Council (CSIC) organized an Interdisciplinary Thematic Platform (PTI) called Global Health in which more than 400 researchers from 144 research groups from various specialties collaborate to address the challenges posed by the coronavirus, from the social to the therapeutic.
Through this platform, different CSIC researchers, university professors and hospitals in Spain came into contact and were able to put their experience, laboratories and facilities at the service of the best ideas and initiatives, selected by a committee of experts.
Based on this initiative, a multidisciplinary team made up of numerous research groups from different institutes of the CSIC, the UPV and other academic and clinical institutions has presented AG5 as “a novel non-steroidal anti-inflammatory compound with immunomodulatory activity.”
This team has been led by CSIC researchers José María Benlloch (Institute of Instrumentation for Molecular Imaging, i3M, CSIC-UPV), and Pablo Botella (Institute of Chemical Technology, ITQ, CSIC-UPV).
CSIC researchers have pointed out that the main novelty of AG5 is that it initiates a new class of anti-inflammatories. In this regard, they have commented that unlike NSAIDs, AG5 is capable of inhibiting the cytokine storm – one of the most serious symptoms of Covid-9 and other pathologies, associated with the hyperreaction of the immune system – such as dexamethasone. , but adequately preserving innate immunity unlike corticosteroids.
The researchers of this new component have added that this is “fundamental in the early stages of any new infection” because “the body needs to develop a defense response against the new pathogen” and also “in the treatment of numerous types of cancer, in which the suppression of the primary immune response facilitates tumor development”.
AG5 was selected through a careful screening study for andrographolide structural derivatives to improve efficacy and minimize toxicity. The researchers maintain that this new compound is a potential substitute for dexamethasone – and, in general, corticosteroids – with much fewer adverse effects and toxicity and also preserving the innate immune system, they have insisted.
In vitro tests have shown that AG5 is an inhibitor of caspase-1 – an enzyme involved in the maturation of mediators of the immune system – and capable of modulating the immune response in inflammatory processes associated with bacterial and viral infections.
Furthermore, the therapeutic efficacy of AG5 has been demonstrated in different animal models of inflammation (zebrafish, mouse), with and without associated viral infection. For example, AG5 is able to inhibit the cytokine storm in humanized mice infected with the SARS-CoV-2 virus without completely suppressing the immune response.
The research team hopes that AG5 will also be very useful in the treatment of chronic inflammatory diseases such as rheumatoid arthritis, Crohn’s disease, lung inflammation and fatty liver disease.
AG5 has also been proposed for the prevention and treatment of cytokine storm in T cell therapy (CAR-T) for cancer. The results have led to a Spanish patent approved in 2023, which is currently in the extension phase in Europe and North America. Another European patent has recently been filed.
Currently, preclinical research with AG5 is almost complete, including toxicological study in different validated animal models and scale-up for industrial production of this drug is ongoing. In 2024, the research team plans to apply to the Spanish Agency for Medicines and Health Products (AEMPS) for phase I and II clinical trials in therapy for fatty liver disease.
AG5 is a synthetic sulfonic derivative of andrographolide, the active ingredient of the plant Andrographis paniculata, endemic to certain regions of India, Sri Lanka and other areas of Southeast Asia.
This work has been supported by the NextGenerationEU Recovery and Resilience Mechanism through the PTI Global Health Platform of the Higher Council for Scientific Research (CSIC), and by the Generalitat Valenciana through the program ‘Urgent aid for research projects, technological development and innovation (I D i) due to COVID-19’ with different projects, whose main researcher is Pablo Botella (ITQ).
Likewise, it has been funded by the SUPERA COVID-19 FUND (whose main researcher is Dr. Jesús San Miguel, Clínica Universidad de Navarra), and by the Severo Ochoa Center of Excellence Program of the Institute of Chemical Technology (ITQ, CSIC-UPV). .
Participating institutions
