Pier Paolo Sainaghi
Rheumatoid arthritis (RA) is an autoimmune disorder, characterised by inflammation of the synovial (joint-lining) membrane, which affects 1% of the population. If not treated, it can lead to joint deformity and permanent disability. There is not yet a cure for RA but prompt treatment with anti-rheumatic drugs (DMARD) can slow down its development, protecting joints from permanent damage. In the event that this early treatment is not successful, a second-line treatment can be adopted with biotechnological “pharmaceuticals” – these are very expensive but also extremely effective, as they work on blocking molecules that play a major role in damaging the joints. Unfortunately, however, although this approach is both therapeutic and targeted, only 40% of patients with RA enjoy a remission of symptoms with the treatment; around one third of patients do not go into remission, and thus end up shifting from one treatment to another, during which time the condition worsens. This situation causes a negative impact both for the individual and society as a whole, and calls for urgent action in the form of a personalised treatment for each individual patient (precision medicine).
The FLAMIN-GO project (‘inflammation that goes away’) embraces this approach. The goal is to develop a joint-on-chip to test available drugs on the market and supply an indication of appropriate treatment within 1-2 months of diagnosis. An organ on-chip is a device which can mimic the characteristics of human tissue (in this case, the joint) in every detail. This is possible thanks to the technological advances in micro and nanoscale fabrication. The chip is multifluid for 3D cell culture that simulates the activity, mechanics and physiological response of an organ, thus constituting an in vitro model of an artificial organ.
The joint is composed of 4 tissues, which play different roles in RA. The synovial membrane is the main site of the inflammatory process, while cartilage and bone are later targets of an erosive process which leads to joint deformity. Tissue damage is fostered by the immune system, flowing into the joint via a system of vessels caused by the disease.
The FLAMIN-GO project uses a very complex chip, and 3 different intermediate chips will be built, one for each tissue, just like LEGO blocks (vessel+immune system, synovial+synovial liquid, cartilage+bone), assembled at the end of the project. This chip will host cell cultures from biopsies taken from each patient. Obviously, thanks to the reduced size of the culture cell, with a bioptic sample it will be possible to build numerous chips simultaneously and therefore test many drugs at the same time. This project aims to revolutionise the way we ‘perform medicine’ – not by trying to predict the response to treatment on the basis of biomarkers, but by testing drugs directly on the affected tissues of each patient.
The FLAMIN-GO project will be pursued at CAAD, a research infrastructure that enables profitable partnerships between innovative research centres, the rheumatology department assigned for the biopsies, and the biobank that will keep the biopsy samples used in the clinical study. FLAMIN-GO will also involve departments of excellence from the School of Medicine (DSS, DIMET).
There are a number of key strong points in our project. The first involves the participation of a large-scale international consortium with cross-sector skills in medicine, engineering, materials science, industry and marketing. FLAMIN-Go intends to establish a start-up company, incubated by CAAD, to produce and market the joint-on-chip. A simpler, non-personalised version, could also be of interest for pharmaceutical companies, in order to test new drugs quickly and safely with a more complex model that is nearer to the reality than the traditional 2D cultures or animal-based versions.