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The European project FLAMIN-GO is underway within the potential of precision medicine, a breakthrough for the treatment of rheumatoid arthritis

The acronym FLAMIN-GO of course calls to mind the spectacular flame-colored bird, but also another fire bird, the phoenix, a mythological creature that can rise from the ashes of its own destruction. Carl Gustav Jung claimed that the phoenix has in common with man the ability to be reborn much stronger after a traumatic experience. But this mythical quality is not so far from the vision underlying the brilliant intuition that, starting from today, will see an international team of researchers working together. Led by the University of Eastern Piedmont, several public and private organizations are involved, including the Institute of Nanotechnology of the National Research Council (CnrNanotec) in Lecce, Queen Mary University of London, the Max Planck Institute, the AO Research Institute Davos (ARI) of Switzerland, and high tech companies Trustech, Fluidigm, Enginsoft and regenHU.

But FLAMIN-GO also stands for “inflammation going away”. The aim of the European research project is to develop “tailored” treatment for each individual patient suffering from Rheumatoid Arthritis (AR). The project was awarded funding of 6 million euro in the Horizon 2020 program.

AR is a widespread chronic autoimmune inflammatory disease that affects more than 400,000 people in Italy alone (some 2,900,000 patients in the EU). It is characterized by chronic inflammation of the synovia, which is the membrane enabling the joint to function properly.

As Costantino Pitzalis – Professor and Director of Experimental Medicine and Rheumatology at Queen Mary University, London – explains, “inflammation causes an uncontrolled growth of the synovia, which expands to the point of destroying cartilage and eroding bone tissue. This leads to pain and joint stiffness that, if not treated, can affect the patient’s quality of life, with anatomical damage and irreversible disability. There is also no definitive cure for Rheumatoid Arthritis. Remission of symptoms is more likely when treatment begins early with disease-modifying antirheumatic drugs (DMARD). In case of failure, we move on to second-line therapies, biological therapies (bDMARD) targeting specific cellular and molecular pathways of the immune system that trigger inflammation and cause damage to joints and tissues. However, their high cost compared to conventional treatments does not allow them to be considered as drugs of first choice. “It is clear that identification of the most effective treatment for each patient is an unmet clinical need in the context of Rheumatoid Arthritis. To proceed by trial and error, without proper logic, is certainly not the best way to go, and the delay in defining the most appropriate therapy means that around 40% of patients with this disease fail to achieve improvement, with significant disability and high social costs. And if we add that 10-20% of patients do not respond to any medication in use today, it is clear not only that Rheumatoid Arthritis is a very mixed picture, but also how great the need is to develop and test new drugs “tailored” to the individual patient.

Precision medicine has, in this sense, an extraordinary potential to improve the response to treatment.

Annalisa Chiocchetti, project coordinator and Professor of Immunology at the University of Eastern Piedmont in Novara, says “FLAMIN-GO was designed precisely with the intention of opening up a new pathway towards personalized medicine in the treatment of Rheumatoid Arthritis. The goal is to provide an organ-on-chip solution (OoC) whereby the best drug on the market for treating each patient can be selected, which will also support the development of new drugs. This solution will be based on the design and production of a multi-compartment microfluidic platform for 3D culture and perfusion of all joint tissues relevant to the disease. It will be focused on the synovia and synovial fluid, but will also include the immune system (blood vessels and leukocytes), as well as cartilage and bone, which are the most damaged tissues. The Translational Research Centre on Autoimmune and Allergic Diseases (CAAD) of the University of Eastern Piedmont will play an important role throughout, since the platform thus implemented can be used to study the molecular basis of each patient’s disease.

Equally significant will be the contribution of TecnoMed Puglia, the “technopole for precision medicine”, based in CNR-Nanotec in Lecce. In the words of Giuseppe Gigli, Director of CNR-Nanotec, “the FLAMIN-GO Organ-on-chip platforms will be developed in our labs. TecnoMedPuglia was founded to boost research in the field of precision medicine, with innovative approaches based on nanotechnology and the translation of results to the patient’s bedside. The challenge is ambitious, but the recognition of the European Community is important for us and encourages us to pursue the path we have taken.”

Alessandro Polini and Francesca Gervaso are researchers leading the CNR Nanotec team. As they put it, “the technological approach of FLAMIN-GO will be a bit like building with LEGO: each brick, corresponding to a micro-articular tissue, will be developed and validated independently, but will connect readily to others to build a complete chip. Starting from the biopsies of individual patients, this model will aim to replicate each AR patient’s joints, with the goal of testing the most appropriate, precisely-customized treatment.

In conclusion, the potential of FLAMIN-GO bodes well for the development of new treatment pathways designed to fit each patient, and may represent the much-desired turning point, both clinical and pharmaceutical, in the treatment of Rheumatoid Arthritis.

Lia Rimondini, researcher in the Piedmontese Team and Director of the Department of Health Sciences, University of Eastern Piedmont, the institution leading the project, explains. “In short, FLAMING-GO has the potential to offer hope for new patient-designed treatment pathways, and may represent that long-desired clinical and pharmaceutical turning point in the treatment of Rheumatoid Arthritis. It also provides a methodological base for the development of personalized treatments for other diseases. In a word, a true excellence of European and Italian research, of which we are extremely proud.”