Regenerative medicine: EuroNanoMed nanotech from bench to bedside

Regenerative medicine: EuroNanoMed nanotech from bench to bedside

Ignacio Baananate, co-ordinator of EuroNanoMed 3, explains how the network is evolving and discusses the last calls for innovative research projects in nanomedicine.

Established in 2008, EuroNanoMed (ENM) is a platform in which national and regional research funding programmes join together with the goal of creating and funding collaborative research and innovation projects that can convert research in nanotechnology into practical gains in regenerative medicine. EuroNanoMed supports multidisciplinary and translational research and innovation projects that cover: regenerative medicine, diagnostics and targeted delivery systems.

EuroNanoMed III (2016-2021) is the new ERA-Net Cofund Action on Nanomedicine under Horizon 2020 that will build upon the achievements on its predecessors to support the European nanomedicine regenerative medicine research community.

Speaking to SciTech Europa Quarterly, Ignacio Baanante, co-ordinator of ENM 3, explained how the platform is evolving and discusses the most recent Call, which focuses on regenerative medicine, diagnostics, and targeted delivery systems.

What have been the biggest developments experienced by EuroNanoMed over the last decade, since its first instalment and through to version 3?

In my view, the big success of EuroNanoMed comes from the creation of a European Research Area in nanomedicine. ENM is something of a reference point for scientists and companies working in the field. The programme is unique as it is the only funding programme devoted to nanomedicine at the European level as well as at the national level (with a few exceptions); it is the only niche where the nanomedicine community can find opportunities (as most of the funding agencies in Europe only launch bottom-up calls).

This community has been growing over the last decade. The first call, which was launched in 2009, received 24 proposals, while a joint call in 2017 saw 151 proposals being submitted. This was only made possible through the support of European Commission, the collaboration with the European Technology Platform in Nanomedicine (ETPN) and, of course, ENM partners (the funding organisations that are part of ENM). Some of these partners have been a part of ENM since the beginning, while others have left the programme and others still have recently joined. Currently, we consist of 27 partners from 22 different countries, and in 2018 two new countries joined the programme (Czech Republic and Bulgaria).

Looking at the research environment in which EuroNanoMed sits, do you feel that more is now being done to aid the transformation of fundamental research into pre-clinical and clinical stages and to accelerate product development of regenerative medicine? What more do you feel could be done to help here, and how can project leaders ensure their research has a commercial impact?

One of the main objectives of ENM 3 is to bring research result to markets and clinical applications. Since the first joint call of ENM 3 (which occurred in 2017) an effort1 has been made to involve more SMEs and large companies and clinicians in submitting innovative research projects in the field of nanomedicine. The different percentages of the type of participants has been maintained, but taking into account the large number of projects received it means that a great inclusion of applicants from such categories as SMEs, large companies, hospitals and health care settings has also been achieved.

The direct effect of these measures is that fundamental research projects simply don’t get funded. This is evinced from the analysis of the outcomes of the independent evaluation process, whereby the evaluation of projects is conducted via peer review and then a final independent peer review panel. From this, we have seen that those excellent projects with no clear future do not receive funding. Nevertheless, the majority of projects that are funded start on TRL 3, with a lower number of funded projects being at TRL 4 and 5.

We will see the results once the three year project has ended, but at least it is well understood that even if a given project demonstrates excellent science but it is nevertheless clear that it will never reach the market, or patients, or that regulatory approval won’t be granted, then this project will not receive funding.

Following on from this, how do you feel Europe compares on the international stage when it comes to the commercialisation of research and the development of new regenerative medicine?

While this is not necessarily my area of expertise, it is no secret that Europe is behind other international competitors when we talk about the development of research results. Europe needs to place more emphasis on reducing the time-to market of new drugs and investing in product development. That could make all the difference when it comes to competing with the USA, South Korea, and Japan.

Europeans investors, venture capitals and business angels tend devote their investments to classical financial options (such as housing, communication, and so on). We therefore need to change our mentality, and that takes time.

Nanotechnology programmes at the national level are somewhat lacking, particularly when it comes to nanomedicine, which often does not feature in national calls etc. How do you feel national level support can be enhanced moving forwards? Do you feel that the apparent lack of support is a result of a concurrent lack of knowledge/information on how nanomedicine can address a number of unmet clinical needs?

As I have mentioned, most ENM partners don’t have a national programme on nanomedicine, but that is not necessarily to say that this is due to a lack of information/knowledge. And that is because, first, they support ENM with national funding (to support applicants in their respective countries and their research and development systems) and second because this is part of their own R&D system.

Many funding organisations only launch bottom-up calls, where any medical area or technical approach could fit in. Nanomedicine projects are not excluded in these bottom-up calls and they do get funded.

Nowadays, nanomedicine is very widespread, and so even in a country where the R&D system or strategy envisages focused calls and none of them are for nanomedicine specifically, they are not excluding nanomedicine in the other programmes either. As an example, and based on my experience in other European programmes, we have seen in recent years how the number of research projects applying for such calls using nanomedicine has increased. This is the case, for instance, in E-Rare (ERA-Net on Rare Diseases), Neuron (ERA-Net on Neurosciences) and the recently-launched ERA PerMed (ERA-Net on Personalised Medicine) which is also co-ordinated by ISCIII, our institution.

Nanomedicine as a regenerative medicine for cancer treatments is just one area which has a huge potential. Could you describe some of the main benefits nanomedicine can bestow here?

About 40% of the projects received and 40% of the projects funded (there is a correlation) in EuroNanoMed calls are about cancer.

Conventional therapeutic approaches to treat cancer involve the use of radio‐ or chemotherapies. Radiotherapy is a complex, expensive and invasive method that causes multiple side effects, while chemotherapeutic drugs show low efficacy due to the difficulty in getting sufficient local drug concentration inside solid tumours to induce the required lethal effect.

These drugs have low specificity and it is necessary to use high doses in order to achieve therapeutic effects, which is the main drawback as this can induce severe side effects. For this reason, chemotherapy sessions are spaced out, and tumor cells use this time to recover, mutate, develop drug resistance, proliferate, and create metastases.

The benefit of nanomedicine is that it results in targeted therapies. Nanoparticles could be designed to be cancer cell-specific or cancer biomarker-specific, meaning that they could be used for early detection or treatment.

Nanocarriers (lipid-based, polymer-based, inorganic, viral and drug-conjugated nanoparticles) are suitable for delivering chemotherapeutic drugs to the target tumour tissue, meaning that toxicity to healthy cells is significantly low and dose-level is also kept to a minimum. Other approaches in nanomedicine include photothermal therapy. This refers to treating cancer by the targeted delivery of biocompatible photothermal nanoparticles and heat to the site of interest without damaging the surrounding healthy tissue.

Nevertheless, there are many obstacles that nanoparticles still face in clinical therapies:

  • Renal, hepatic or immune system clearance
  • Lower permeability and retention effect in clinical tumours than in murine models
  • Interstitial hydrostatic pressure that inhibits nanoparticle extravasation
  • Poor diffusion inside solid tumours, and
  • Panoparticle trapping by cellular endosomes

EuroNanoMed’s ninth Call focuses on regenerative medicine, diagnostics, and targeted delivery systems. Why were these particular topics chosen, and what are your hopes for this call?

Those experts consulted during the second phase of ENM phase agreed that the open bottom-up approach used for the ENM calls so far is the right one in order to contribute to increasing innovation and translational research in the field of nanomedicine. It was also agreed that this is also complementary to Horizon 2020 calls, which are mostly disease-oriented. In addition, the choice of specific topics to be addressed in a focused call could lead to misalignments with national/regional strategies and therefore discourage the participation of a number of national/regional partners in the Joint Transnational Call (JTC). Therefore, ENM Joint Calls are open to the three priorities described by the European Technology Platform on Nanomedicine: targeted drug delivery, diagnostics, and regenerative medicine.

The results of the Joint Calls depend on the availability of funds from national and regional funding organisations. Unfortunately, at the end of the evaluation process we usually end up with more projects that are worth funding than those that we are able to fund. We nevertheless hope to meet the funding demands from the best projects – see Fig. 1 for an idea of ENM trends.

In future Calls, we hope that more countries will be able to join the Call for projects (such as the Czech Republic and Bulgaria) and regarding those that continue to participate, we hope they will be able to commit more funding.

In a more general sense, how do you feel EuroNanoMed will evolve in order to meet the future demands of regenerative medicine?

The overall expected impact of EuroNanoMed III is a thorough, lasting and forward-looking alignment of current European funding organisations with the goals of creating synergies and coherence in nanomedicine research at national and regional level and favourable conditions for an increased uptake of nanomedical technologies into industrial medical products.

Nanotechnology applications for healthcare are having a tremendous impact on Europe’s industrial sector and international markets. Nevertheless, more efforts and partnerships between EU countries to achieve better results, treatments and diagnostic tools are needed. A significant impact on Europe’s nanomedicine is expected by the joint implementation of transnational funding within ENM. Since the main focus of funding will be on application-oriented research, it is expected that this will tremendously improve coherence and generate stronger synergies in the thematic area.

ENM III will go beyond the efforts made in ENM I and II in this respect by putting in place activities towards creating favourable conditions for an increased application of projects results and its uptake into industrial medical products.

References

  1. ‘Effort’ refers to: (i) improving the dissemination strategy towards relevant stakeholders and target groups; (ii) emphasise the translational approach of the projects to be submitted; (iii) impact evaluation criterion has also been upgraded as in Horizon 2020; (iv) a more balanced peer review panel.

Ignacio Baanante

EuroNanoMed Co-ordination Unit

National Institute of Health Carlos III (ISCIII)

Spain

+34 91 822 2576

ibaanante@isciii.es

Tweet @euronanomed

http://euronanomed.net/

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