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Dr. Pere Joan Cardona

Founder of Manremyc


Dr. Pere Joan Cardona, co-founder of Manremyc along with Dr. Cristina Vilaplana, Isabel Amat and Jaume Amat. He is head of research for a revolutionary product to fight tuberculosis. This spin-off of the Germans Trias i Pujol Health Sciences Research Institute will launch a nutraceutic targeting this bacillus on the Indian market in the second half of 2015, which may in the long term eradicate this disease. Pere Joan Cardona participated in the BioEmprenedorXXI awards.


Nyaditum resae® is a food supplement that has been developed from a bacteria in the same family as the one that causes the tuberculosis. It not only reduces inflammatory response but also “educates” the host’s immune system to not consider tuberculosis a danger. In fact, this supplement doesn’t trigger an immune response to the bacteria at all; it generates specific cells to regulate against the tuberculosis bacilli in order to avoid excess inflammation, which is what really leads to development of the disease. The product will be manufactured in a fermentation plant in Catalonia and be lyophilized in Barcelona, and then the company marketing the product will transform the concentrated product into the format most fitting the Indian market.

Each year, tuberculosis kills 1.5 million people around the world, 100 million new infections are registered and 8 million people develop the disease. Although the death rate in Catalonia is very low, each year 1,200 infections develop into the disease and approximately 10,000 new infections occur.

It seems like you’re fighting tuberculosis through a paradox?

It’s a revolutionary idea because we looked at tuberculosis as an infection and we asked ourselves what would happen if this infection didn’t progress towards the disease. Then it would be fine: we’d have the infection and that’s it. Working to discover what made it go from one stage to the other, we reached an experimental model that imitated a lesion of the disease in humans. That’s when we realized, to our surprise, that the shift was caused by excessive inflammatory response to the bacillus. Unlike previous protocols, which provoke a strong immune response against the bacteria, we saw that this was dangerous and that the best way to avoid developing the disease was to ignore the bacillus.

Ignore it and work with regulatory cells?

The idea is to find a new approach based on building up tolerance against the bacillus, or to generate specific regulatory cells against the tuberculosis bacillus to prevent it from causing excess inflammation. Herein lies a new paradox… we previously understood regulatory cells to be enemies, inducing the disease because they reduced immune response. But now we’ve proven that too great an inflammatory response attracts neutrophils and these serve as a platform helping the bacillus grow out of control, leading to the disease. We started what is called low-dose tolerance, with dead tuberculosis bacillus, and realized that it was working, that it provided protection.

Paradoxes that make Nyaditum resae® an innovative way to treat the disease.

Yes, it’s revolutionary. We’ve been lucky in that two groups have arrived to this conclusion from other perspectives, looking for biomarkers in people with the disease, and have seen that the people who get the sickest do so due to an exaggerated response. And this is the concept that is starting to be the focus of other studies. Our contribution has been to explain how this excessive inflammation causes the infection to become the disease experimentally and physically.

But this supplement acts on different targets.

For now, we’ve carried out a clinical trial and shown, on one hand, that our product doesn’t have any adverse effects and, on the other, that we have a biomarker (the specific regulatory cells) that will prevent the infection from developing into the disease. This cross-immunity between environmental and tuberculosis mycobacteria was already known, but it was thought to serve to destroy the bacillus, not build up tolerance.

And why a food supplement?

For two reasons: because the regulatory requirements are much simpler and because it will make the product much more affordable than a drug. We decided to look for an environmental mycobacterial bacterium so the risk would be lower and have beneficial effects. We had to find a fast-growing mycobacterium to make the industrial manufacturing as affordable as possible, under €5 for the 14-day treatment. This process led us to Mycobacterium manresensis (which belongs to the fortuitum group). It is a mycobacterium found in water, in this case that of the Cardener River, and can thus be considered a food product. We’ve proven that, when administered in the right dose for the right amount of time, this dead mycobacterium generates a regulatory effect.

Would this supplement only affect people who already have the bacillus?

No, it also works for people who haven’t been infected. Although the significance of this is relative now because of the high infection level in the countries where we expect to market the product, where the vast majority of people are already infected.

And if the person has developed the disease?

It also works in this case. After completing the antibiotic treatment, patients can take our product to avoid relapse.

But if it can be taken as a preventative measure, could we be looking at a chance to eradicate tuberculosis?

Of course, but that’s another level of application. For that to be possible on a mass scale, we’d have to irrefutably prove that it has this effect on a populational level. This is why we are also looking for investors to sponsor clinical trials. And once we’ve proven its efficacy rate, then we can talk about one of the great solutions to the problem of tuberculosis.

Will Nyaditum resae® replace antibiotics?

One of the key focal points in the EU is to increase use of this type of food supplement (in this case an inactive probiotic) in order to avoid overuse of antibiotics. Right now there is a significant part of the population that is resistant to antibiotics, so we have to find new solutions. But this requires a lot of funding. For now, we’re starting in India because it has the largest population with tuberculosis. We’ve been there a few times now and, of the ten companies we’ve met with, there are three or four that are quite interested. We’re working to close a deal through an intermediary, Inquve, which manages products launched onto the Indian market.

When do you expect to have the product on the market?

Hopefully by the end of the year.

Only in India? Haven’t you explored other markets?

Yes, for now only India, but we are looking into other markets in Asia: China, Indonesia and Thailand, as well as South Africa, which also have high tuberculosis rates.

You were talking about marketing the product through another company. Have you thought about dealing directly with public health systems?

To start off, we’re only looking to reach agreements with private companies, although we haven’t discarded other options. What is clear is that we need sponsorship from social organizations to carry out clinical trials to prove the efficacy rate of our probiotic and in what percentage of the population. We want to put the product on the market as soon as possible, because we can prove that it provides protection, but we’ll have to continue working even after it is on the market.  And we can do this through sponsors or the company marketing the drug funding clinical trials.

Yours is a good example of how a spin-off can generate knowledge and business.

Spin-offs are an interesting instrument and a good mechanism for technology transfer and to promote ideas that come out of basic science. It’s difficult for large companies capable of attracting projects to spring up in our country. Small businesses led by entrepreneurs are much more feasible. People get involved in the ideas, search for ideas, and that pushes aside the fear of failure and makes you see it as an interesting experience you won’t repeat in a new project. Failure shouldn’t be hidden; it should be explained. And we have to live without fear or reluctance. And public institutions must think this way and promote entrepreneurial initiatives as a way to generate knowledge.

But that requires great change. Can institutions take this cultural shift onboard?

Institutions have already begun to look at spin-offs with less suspicion, giving them support through bodies like Biocat and ACCIÓ, but we have to continue down this path. We have to promote a more open mentality, more daring, more pioneering, because success is more likely with these traits. Although it’s true that we must also be vigilant in ensuring research and business opportunities. This is why we need scientific boards and careful monitoring in addition to financial and structural support… We must all, in the public and private sectors, have a clear idea that we need to promote and invest in research for one key reason: because it is important and necessary to move forward as a country. 

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