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Repurposing finds new health-giving uses for old medicines

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By VITTORIA D’ALESSIO

Drug discovery is slow, expensive and often ends in failure, so no wonder scientists are exploring new ways to medicate disease. One source of hope lies in ‘drug repurposing’, where new uses are found for established medicines.

For example, the humble dexamethasone proved a lifesaver during the Covid-19 pandemic, significantly reducing mortality in critical patients who are put on oxygen or ventilators.

Yet the drug was not developed with a killer virus in mind. Dexamethasone became a licenced medication half a century before the advent of Covid-19, and it was designed to help patients with swelling and severe allergies. The serendipitous discovery that it also kept people alive during the coronavirus pandemic was the result of the scientists working at lightening-speed in the field of “drug repurposing”.

Drug repurposing is not just some niche area of scientific exploration. Finding new uses for pre-existing medicines is becoming a major focus for research bodies the world over, with Europe leading the way.

Drug discovery

‘We’ll still need to discover new drugs, but drug repurposing is going to play a growing role in medicine, and it’s going to be particularly important in the area of rare diseases,’ said Anton Ussi, coordinator of the recently launched, €22.6m Horizon-funded REMEDI4ALL project. ‘It could make the difference between having no drugs to treat a debilitating condition to having a repurposed one that has a big impact on quality of life.’

There are clear benefits to repurposing ‘old’ drugs to tackle diseases for which treatment is lacking. Developing a drug from scratch is a huge undertaking. The average cost is over €1 billion, and typically it takes more than decade for a new medicine to complete its journey from initial discovery through clinical trials and to the marketplace. What’s more, many therapeutic molecules that look promising near the start of the research process are eventually ditched because they’re found to be either ineffective or unsafe.

‘By turning our attention to an existing drug, in optimal circumstances, a new treatment can be found in just a few years and for a fraction of the cost – rather than many years of research and tens of millions, even hundreds of millions, of euro,’ said Mr Ussi, who is based at EATRIS, the European infrastructure for translational medicine.

Many steps

Drug repurposing may bring efficiencies to drug development, but many steps still stand between a researcher’s light-bulb idea and a boxed medicine. Clinical trials are needed to establish a medicine’s effectiveness at treating the new condition. The drug must be deemed safe for its new application. Dosage protocols must be established. Patient advocacy groups must be consulted. Regulatory authorities must be satisfied. A manufacturer and distributor must be found.

However, patchy coordination between academics and institutions working in the field is stymying progress. Teams are working on their projects in silos and expertise is going untapped. As a result, many researchers working on a promising idea simply give up.

Elaborating, Mr Ussi said, ‘There are islands of great research activity but it’s difficult to take your research to the end without outside professional help.

‘Take the example of an expert clinician who knows anecdotally that a drug used off-label (for an unapproved purpose) slows down a disease,’ he said. ‘This clinician may want to validate their hunch so the drug can become authorised to treat that disease, but they don’t have access to the broad range of experts and disciplines needed to do so. Because of this, most would-be drug developers run out of capacity.’

The aim of REMEDI4ALL is to catch enthusiastic researchers and research groups before they fall. ‘We want to make the world of drug repurposing more understandable,’ said Mr Ussi. ‘We’re creating development teams that can get to grips with the specific requirements of a project and help move the process along to completion.’

Through its ‘transparent and predictable pipeline’, REMEDI4ALL will bring experts in all areas of drug development from all over the world into one space.

Repurposing process

‘Everyone who has a role in the repurposing process will become part of our network,’ said Mr Ussi. ‘Our vibrant community will be able to help researchers execute their projects at any phase of development. Our vision for 10 years from now is that drug repurposing will work efficiently, so projects with real potential don’t get stuck in bottlenecks.’

Another Horizon project, the brand new REPO4EU describes itself as a “platform for precision drug repurposing”. REPO4EU will be working closely with the REMEDI4ALL group to make the process fast, cost-effective and patient-centric. With ambitions to turbo-boost the world of drug repurposing, they will address unmet medical needs in all disease areas.

Funded by the Horizon Europe programme to the tune of €23 million, the project also aims to develop a permanent European infrastructure that can serve as a resource for every potential researcher or small-to-medium-size enterprise interested in drug repurposing. But that’s where the similarities between the two projects end.

The “high-precision” REPO4EU approach to finding new applications for registered drugs (based on a seminal study from 2015 on the relationships between diseases) is predicated on the finding that, when all human diseases are plotted on a network map, disease clusters emerge.

Significantly, diseases in a given cluster share the same risk genes. In other words, specific gene mutations can trigger a cascade of events that can give rise to any disease from within its cluster.

The REPO4EU team position is that a disease should therefore be described less as an “organ malfunction” (say, heart or kidney failure) and more as a precise “mechanistic” problem (i.e. focused on the mechanisms giving rise to disease). This is nothing short of a paradigm shift.

Precision cure

In their quest to find new purposes for established medicines, the REPO4EU researchers are zeroing in on drugs that are known to target a particular mechanism, explained Prof. Harald Schmidt, coordinator of REPO4EU and professor of pharmacology at Maastricht University. Next, the team will design high-precision clinical trials to ‘rapidly and safely cure’ conditions that share this mechanism.

‘Patients will be selected based on symptoms and, more importantly, the detection of the disease mechanism. This means every treated patient is expected to benefit,’ said Prof. Schmidt.

He believes the project will herald the end of the organ-based structure of medicine. ‘Right now, we hardly understand the cause of any chronic disease at the level of genes and cellular signalling, and so we’re left with chronically treating symptoms with low precision and limited patient benefit.’

He added: ‘The traditional, reductionist “one disease, one target, one drug” dogma has had its time. Ours is a completely new approach to medicine, and our team is totally convinced by it. Network medicine will redefine what we call a disease, how we diagnose it, and how we cure it – not just treat it.’

Research in this article was funded by the EU. The article was originally published in Horizon, the EU Research and Innovation Magazine.  

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Health & Wellness

Making face creams from coffee beans as cosmetics get greener

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By Tom Cassauwers

‘Plant ingredients have always been used in cosmetics,’ said Heiko Rischer, head of plant biotechnology at VTT, a Finnish research centre. ‘But in recent years, there’s been a revived interest in plant-based compounds. Consumers are interested in greener and more sustainable ingredients.’

Today, most of the key ingredients used in the €80 billion European cosmetics industry are synthetic or animal-based or taken from wild plants. Producing these ingredients sometimes includes solvents or processes that are unsustainable and are becoming less popular with consumers. Harvesting wild plants also puts natural ecosystems under pressure.

Rischer and other European scientists are investigating how to get more natural and sustainable plant-based ingredients into cosmetic products.

Ecosystem pressure

The EU-funded InnCoCells project that VTT is coordinating is creating alternative ingredient options by growing plants or plant cells for use in cosmetics in a sustainable way.

‘We grow plant cells and organs in bioreactors,’ Rischer said. ‘But other partners grow the entire plants in aeroponics and greenhouses or in the field.’

InnCoCells is researching the commercial production of innovative cosmetic ingredients from plants such as basil or aromatic ginger.

‘Our work is currently in a bio-prospecting stage,’ said Rischer. ‘We evaluate different plant species for compounds. We start from a wide range of potential plants and reduce them over time.’

The team aims to develop up to 10 ingredients to bring to the market within the next three years – although it’s still early days for a project that started in May 2021.

‘Finding our way in this jungle of plant options is a challenge,’ Rischer said.

The focus is on the bio-active compounds in cosmetics, meaning the ingredients that create a desired effect such as anti-ageing of the skin rather than ingredients like stabilisers or fragrances. An essential part of the work in InnCoCells is to have the cosmetics do what they promise in a transparent way.

‘Cosmetics need to open up the evidence, so that products actually do what they claim,’ said Rischer. ‘This would really help the consumer make choices. When we buy food, there’s a lot of information on the package helping the consumer. We need to do the same for cosmetics.’

Coffee creams

In a separate, just-ended, initiative to green the cosmetics industry, the EU-funded Prolific project transformed plant residues into ingredients for beauty products. The team extracted polyphenols from coffee silverskins, a type of compound useful in cosmetics because of its anti-ageing effects on the skin. The polyphenol extract was standardised and used in a prototype face cream.

Normally, polyphenols are already derived from plants. But the compound is extracted through a chemical procedure resulting in waste that needs to be disposed of carefully. The project applied an environmentally friendly method, called subcritical water extraction, which only uses water under very high pressure to extract the polyphenols from the coffee silverskins.

All in all, the Prolific research used a range of new processes to derive useful compounds from agricultural waste of different plant sources such as coffee beans, fungi and legumes.

‘We use a cascading approach,’ said Annalisa Tassoni, the project’s scientific coordinator and an associate professor at the University of Bologna in Italy. ‘We do a first extraction, after which we look at what remains and try to extract another compound.’

Ultimately the residual fibres were used at different stages of production. Three prototype cosmetics were made by Greek partner company COSMETIC including a face cream, toothpaste and even a container jar that was made from plant fibres.

‘We valorise all the parts of the residues,’ said Georgios Tsatsos, general director of COSMETIC. ‘This goes up to the fibres left after the extraction process.’

Plant-based compounds

Several steps need to be taken before these green compounds can reach the cosmetics market. The techniques used by Prolific in processing coffee are close to being introduced into cosmetics production, but the methods need to be scaled up so that plant-based compounds can compete with synthetic ones.

‘There’s a lot playing in favour of this process for coffee,’ said Tassoni, ‘We opened up perspectives, and confirmed that certain techniques really work.’

While it will be difficult to outcompete all of the synthetic techniques in use in the cosmetics industry, Rischer is optimistic about the outlook for more environmentally sound approaches.

‘The cosmetics market is very big and diverse,’ he said. ‘Consumers are demanding more sustainable and green cosmetics, and within our own niche, we can have an impact.’

Research in this article was funded by the EU. This material was originally published in Horizon, the EU Research and Innovation Magazine.   

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In fight against male cancer, caring for mental health is a growing priority

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By Anthony King

At a hotel in the Scottish city of Aberdeen about 20 years ago, urologist James N’Dow and other doctors met a group of men who had suffered prostate cancer to ask for feedback on their care before and after surgery. The clinicians were stunned by the critical, albeit constructive, responses.

‘Frankly, they felt abandoned,’ said Professor N’Dow, who works at the University of Aberdeen. ‘When we discharged them after surgery, we thought their general practitioners were looking after them and their GPs thought we were.’

Minding the mind

Dealing with the emotional and mental toll of prostate cancer has grown in importance along with detecting and curing the disease itself. Prostate cancer is the second-leading cancer among men in Europe and is sometimes mistakenly viewed as a disease only of old age. It caused an estimated 335 500 cases, or 12.5% of cancers, in the EU in 2020.

Prof N’Dow heads an Innovative Medicines Initiative project – PIONEER – on prostate cancer that seeks to improve diagnosis and treatment. A parallel EU-funded initiative called FAITH is developing an electronic application for cancer survivors that could help spot if the “black dog” of depression is stalking them.

‘Depression is a big thing in post-cancer survivors,’ said Gary McManus, who leads FAITH and works at the Walton Institute for Information and Communication Systems Science in Waterford, Ireland.

Four in 10 men who have been treated for prostate cancer say they are anxious or depressed to some degree, with troubles worsening the more advanced the cancer, according to a 2020 study by Europa Uomo, a European advocacy movement for sufferers of the disease. Prostate cancer can increase the risk of suicide.

Stopping the spread

When prostate cancer is caught early enough, a man can be cured. If it spreads beyond the prostate, the cost of treatment is high and delivers minimal benefit. Usually, the disease will spread – metastasize – to the bones and lymph nodes.

‘It is not curable at that stage,’ said Prof N’Dow. ‘We are still picking up too many men with metastatic disease – and this is a failure of the system.’

Without treatment, the average period of survival from prostate cancer that has spread beyond the gland is about 21 months. With some newer therapies, some metastatic prostate cancer patients can survive five years or more.

Even when the cancer is aggressive, if it is restricted to the prostate gland a patient can be cured by surgery or radiation therapy – or a combination. Almost 95% of these patients are still alive up to 15 years after their diagnosis. Treatment can, however, affect a man’s urinary or erectile function.

Prof N’Dow hails recent EU recommendations to screen prostate cancer in men up to the age of 70 using a blood test and magnetic resonance imaging (MRI) scans based on an individual’s risk. Certain men over 50 and those of African descent or with a family history of prostate cancer are at heightened risk from this cancer and should be targeted for early detection.

Tracking the blues

Amid the efforts to improve detection and cures, FAITH’s planned app highlights the heightened focus on the psychological well-being of cancer patients.

Although it is being tested on people who have overcome lung and breast cancer, the app could be made to work for survivors of the disease in other parts of the body including the prostate.

In its study two years ago on anxiety or depression among men who have been treated for prostate cancer, Europa Uomo said 0.5% felt either one to an “extreme” degree and almost 4% to a “severe” extent. Nearly 11% and 28% fell into “moderate” and “slight” categories, respectively.   

A tracker of sorts, the app is being developed by European technologists and cancer doctors working together. The tests are taking place at three hospitals in Ireland, Spain and Portugal.

At home, a wearable watch records movement and sleep patterns that get fed into a phone app. Patients must occasionally answer questions from the app, for example about dietary choices, while a voice module checks for any changes in a person’s speech that may indicate depression.

In all, 27 measurements are being tracked in a bid to uncover which ones could flag a downward trajectory in a patient’s mental health. Performance will be compared against clinical questionnaires that doctors already use to monitor patients.

‘Once the patient is signed out of the hospital, they’re often on their own,’ said McManus. ‘If the hospital gives this app to a patient, doctors can remotely monitor how the patient is getting on.’

The phone app will not send sensitive patient data to the Internet. Instead, an algorithm is updated on the phone and fed back to the development team, which helps improve the app’s performance.

‘We’ll build our algorithm and try to pick out these downstream trajectories,’ said McManus. ‘Then we are basically training the app.’ Eventually, if the app picks up worrying signals, ‘an alarm is raised in the hospital and the patient is contacted,’ he said.

Empowering patients

The mental-health aspect of cancer diagnosis and care needs to be improved across Europe, according to Prof N’Dow, who said that this is a central goal of the European Association of Urology, where he is adjunct secretary general responsible for education.

‘The impact psychologically of the diagnosis or consequences of treatment is huge,’ he said. ‘This is something we understood in PIONEER.’

The project has sought to ensure that treatment comparisons take into account the impact on patient quality of life such as sexual, bowel or urinary function. Also crucial has been to identify those outcomes that matter most to patients.

That is why PIONEER has included patients themselves in discussions aimed at determining key unanswered research questions about prostate cancer.

‘Patients understand what they need,’ Prof N’Dow said. ‘Our job is to improve the lives of the most vulnerable and get them back to the life they knew before it was rudely interrupted by disease. The psychological well-being of the patient and their families should be recognized as central to that.’

Research in this article was funded via the EU. This material was originally published in Horizon, the EU Research and Innovation Magazine.   

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Central Asian Countries Show Commitment to a Cross-regional Approach to Pandemic Prevention

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Government officials representing health, environment, and agriculture sectors from all of Central Asian countries participated in a regional ministerial meeting Protecting Livestock and Preventing Pandemics that took place in Almaty today. The participants reaffirmed commitment to cooperating on One Health–a cross-sectoral approach that aims to help the region prevent future pandemics. The participants signed a communiqué giving a formal start to the development of the Central Asia One Health Framework for Action and a call for joint resource mobilization in support of the initiative.

Managing global health risks requires full cooperation between the livestock, environmental and public health sectors, at the national, regional, and global levels. One Health is an integrated, unifying approach that aims to sustainably balance and optimize the health of people, animals, and ecosystems. It recognizes that the health of humans, domestic and wild animals, plants, and the wider environment are closely linked and inter-dependent.

“The case for collaboration on One Health in Central Asia could not be clearer,” said Tatiana Proskuryakova, World Bank Regional Director for Central Asia. “The region shares many common challenges but also strengths and opportunities that can help the region realize One Health. What we are witnessing now is Central Asia setting an example for other regions and countries on how to work together for future generations’ health and wellbeing”.

The event in Almaty builds on the discussions held during a meeting in Tashkent in July 2022 when participants agreed on the need to prepare the Central Asia One Health Framework for Action that could provide a blueprint for the countries in the region to move forward with concrete actions, as well as would include a roadmap for investments at national and regional levels.

More specifically, the Regional One Health Framework for Action aims to contribute to addressing three high-level goals shared among Central Asian countries: pandemic prevention and preparedness, resilience of food systems, and improving regional trade and the competitiveness of agriculture. In addition, the Framework for Action will identify focus areas and mechanisms for regional collaboration, and include a One Health dashboard to monitor progress, while facilitating policy responses to emerging issues.

“Investing in One Health is an investment in humanity’s future. The proposed investment framework helps governments and development partners to avoid the cycle of panic-and-neglect and direct financial resources. This integrated, risk-based approach requires compliance with international health standards and promotes country ownership, while recognizing its global public goods nature. The vast majority of investments in One Health will also result in significant co-benefits, including improving food safety, preserving biodiversity and reducing GHG emissions” said Martien van Nieuwkoop, the World Bank’s Global Director for Agriculture and Food. “The World Bank is collaborating with several countries in Central Asia on this approach, and we are encouraged by the region’s resolve to work together to invest in One-Health as an important building block for pandemic prevention, preparedness and response”.

The development of the Framework for Action will support regional dialogue between networks of decision makers and technical staff, including epidemiologists, veterinarians, and environmental specialists from the three operational sectors. This will be especially useful in cases of transborder disease outbreaks, as it would enable sharing of information, quick integration of new knowledge, and regional action.

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