Josep M. Grinyó 'We want to establish our protein as a new therapy for autoimmune diseases'

What are the features of the molecule you have developed?

We have made a protein molecule, that is to say, a combination of three protein sub-components with different missions. One part of the protein increases blood solubility so that the molecule can circulate and have a longer half-life; the other two parts of the molecule exert an immunosuppressive action so that the body’s immune response is not so strong. The novelty of this protein is that it contains a part that inhibits cellular immune responses, and another part that reduces the response of T cells, the main protagonists of the immune system. That is to say: we inhibit activation and activate inhibition.

To which diseases could this molecule be applied?

The inertia of our personal backgrounds led us to try it on a kidney transplant model first, and it went well. But the regulatory agencies that test drugs are very restrictive when it comes to assessing the actual clinical value of new immunosuppressants in the field of transplants, as most do not greatly improve short-term outcomes, and long-term beneficial effects are more difficult to prove and can be diluted.

With this in mind, since new biological immunosuppressors have now entered the field of autoimmune diseases and there is great interest, as well as a healthcare and social need, we considered exploring the molecule in connection with autoimmune diseases. Taking advantage of the fact that we are nephrologists, we made a model for the treatment of lupus nephritis, which is a disease that mainly affects young women and shows varying degrees of severity (from slight joint pain) to complications that can affect the nervous system, the heart, the lungs and kidneys. We developed a treatment model and it worked out frankly well, as we were able to objectify its beneficial effects. In the case of nephropathies, it is possible to quantify activity parameters, and one of these is the excretion of proteins by the diseased kidney. Instead of a semiqualitative assessment of how a person feels, we can objectively measure a protein that should not be present in large quantities were it not for the disease. In this case, what we have seen is that our molecule reduces this presence in a very significant way, at the same level, for example, as cyclophosphamide, a very toxic drug whose administration entails paying a very high price in terms of adverse effects. Our molecule gives excellent results. This has led us to look into another disease related to the mechanisms through which lupus develops: rheumatoid arthritis. We want to work on this and show that this molecule is also capable of alleviating joint injuries.

How would the molecule help treat these diseases?

Therapeutic efficacy would be the same as that of these highly toxic drugs and, furthermore, the long-term administration of our molecule could prevent recurrence. In these types of autoimmune diseases, which also have a high inflammatory component, the triggering factors of relapses are not well known (it can be a cold or a viral infection among others). These diseases are currently something of a losing game in the sense that many times patients do not fully recover and do not return to the state they were in before the relapse. Therefore, reducing recurrence is also a necessity.

Over the last few months the project has been awarded two F2i-FBG grants and has been selected to participate in the CaixaImpulse programme. How will you invest this money and resources?

These grants are vital to us. We were awarded the F2i Valorization Fund to explore an in vitro model of psoriasis skin damage. The Mentor in Residence has allowed us to incorporate an expert who has helped us to plan and structure what is called ‘the regulatory guide’ (generation of therapeutic evidence, safety demonstration, requirements of potential licensees, etc.).

The CaixaImpulse programme will help us a lot, because we have decided to develop a rheumatoid arthritis model. Having a proof of concept of efficacy on lupus nephritis and a successful rheumatoid arthritis model would help us to establish our protein as a useful protein for the general treatment of autoimmune diseases. This evidence would strengthen our ultimate goal, namely, providing a broad spectrum of indications that could be very helpful to deal with these autoimmune diseases.

What will you do with this molecule?

We believe that the most promising approach is to create a license, either directly with a company at the current stage or through the creation of a university spin-off. On the one hand, as a spin-off, we should see how far we can go on our own, depending on the funding we can get. On the other hand, there is the possibility of finding a pharmaceutical company that is interested enough to undertake the whole preclinical development.

At this point, for instance with regard to lupus, there are no more proofs of concept we can perform. In some diseases, efficacy must be demonstrated preclinically in animals that are close to humans, such as primates. Lupus does not exist in primates, therefore the next step is to study toxicity in higher mammals and then in humans. In a way, this allows us to benefit from immediacy. If it were not toxic, then we could consider moving on to clinical testing. This also happens in the case of rheumatoid arthritis, which needs to be examined through a proof of concept and then toxicological tests.

What is the importance of knowledge transfer in your opinion?

Research must always convey knowledge: it is based on knowledge and must lead to more knowledge. And knowledge materialises in institutions through the consolidation of research groups, the raising of competitive funds, the start of new research lines, and the generation of knowledge. Knowledge transfer should be useful right from the research stage. For instance, if knowledge is transferred to the pharmaceutical industry this generates returns that feed back into the system creating more opportunities for research. For many years, the scientific community only considered the intrinsic value of knowledge for knowledge. At one point, some scientific communities decided that biological and biomedical scientific research should result in a real application so that patients, healthcare systems and, ultimately, society could directly benefit from it. In the field of rheumatology, for example, what was done twenty years ago had nothing to do with what is being done now. In the past everything involved anti-inflammatory drugs that did not essentially interfere with the course of the disease but only served to reduce pain and inflammation. Today, the innovations derived from research make it possible to interfere a great deal and really modify the course of the disease. There are no miracles, but we see significant improvements. The ultimate beneficiary of all this is always society, and I believe that the role of the institutions is fundamental in this.