CF Syndicate in Antimicrobial Resistance
The CF Syndicate in AMR aims to get more antimicrobial drugs to cystic fibrosis patients faster.
The Cystic Fibrosis Trust and Medicines Discovery Catapult (MDC) announced a joint partnership to form the ‘CF Syndicate in Antimicrobial Resistance (AMR)’ in 2019. Its aim is to speed up the drug discovery process - from the discovery of a new antimicrobial drug to it reaching people affected by cystic fibrosis (CF) in the clinic, using the combined expertise of its members and the wider research community.
What is the CF Syndicate in AMR?
Enabled and managed by MDC and the CF Trust, the CF Syndicate in AMR is a partnership of university and hospital-based researchers, and researchers from biopharmaceutical and biotech companies who are working on understanding and treating bacterial, fungal and viral infections in CF and other diseases. Two members of the CF community are also members of the partnership.
MDC is an independent not-for-profit organisation that is funded by Innovate UK (the UK’s innovation agency). MDC helps UK companies and researchers to discover new medicines and bring them to patients faster, by providing access to scarce knowledge and expertise.
Working together the CF Syndicate in AMR aims to get more antimicrobial drugs to CF patients, faster. It is doing this by helping to overcome existing hurdles in drug discovery.
Why aren’t there more antimicrobial drugs to treat cystic fibrosis?
- Bugs behave differently in people with CF
- Increasing antimicrobial resistance
- The time, expense and resources involved in developing new drugs.
To read more about these topics, see the bottom of the page.
Why is the CF Syndicate in AMR the answer?
To break the impasse on developing effective antimicrobial drugs for people with CF, MDC and the Trust believe that if they can overcome common barriers that are faced in the development of new antimicrobial drugs, then the rest will follow – bringing drugs that outwit the bugs in the CF lung to the clinic sooner. If the researchers can be successful in treating CF lung infections, then the same approaches may be able to be applied to tackle infections in general.
What progress has the CF Syndicate in AMR made so far?
The Trust and MDC are working together to drive and co-ordinate this partnership. Underpinned by management and expertise from MDC, a Steering Committee of the CF Syndicate in AMR has been formed, bringing together many researchers, clinicians and companies to work together as a partnership. The Steering Committee have developed a research agenda. This is currently focussed on enabling greater access to CF samples, defining preclinical screening and testing pathways, as well as activities that ensure that any drugs developed meet both clinical and patient need.
The CF Syndicate in AMR also aim to provide a louder voice to demonstrate the need for this type of research and attract more research funding to continue this work.
More detail on why there aren't more antimicrobial drugs to treat cystic fibrosis
People with CF are susceptible to developing lung infections. These include the known bacteria such as Pseudomonas aeruginosa and NTM, fungal infections such as Aspergillus fumigatus and virus infections such as RSV or ‘flu. Once these infections adapt to the CF lung environment they can be extremely difficult to treat. In some cases, the bugs are becoming resistant to the strongest drugs that we have available. Note that bacteria, fungi and viruses are collectively known as microbes – hence the wider term of ‘antimicrobial resistance’ rather than ‘antibiotic resistance’ which only includes bacterial infections that are resistant to treatment.
The reason why people with CF are susceptible to infection – and why the infections are so difficult to treat is connected to the damaged CF gene that causes cystic fibrosis. On a practical note this means that most effective new antimicrobial drugs for people with CF will need to take into account the local conditions the bug is growing in and how the bugs are adapted to these conditions. This is a different set of requirements to drugs required to treat infections in people who don’t have cystic fibrosis.
Treating infections in people without CF is a world-wide health concern, as many infections are becoming resistant to the latest drugs. To address this, the Government have identified tackling antimicrobial resistance as a top health priority, regularly making research funding available to achieve this.
Antimicrobial therapies are prescribed iteratively. People with an infection will start off with a mild antibiotic with few side effects. If this doesn’t treat the infection, then drugs on the next ‘step up’ are prescribed; stronger drugs that may have more side effects. However, there are not an everlasting number of options for doctors and pharmacists to reach for. More and more people are being treated with ‘last resort’ antimicrobials as a consequence of resistance to the weaker antibiotics, and more last resort antimicrobials are needed.
Drug development to make these last resort medicines is expensive. Millions of pounds are spent over many years to develop drugs, and the current economic model is that the companies recoup those costs when the drugs are licenced. The payments companies receive are based on the number of drugs used, so the more they are used, the better the chances are of companies re-couping their costs. For big companies with lots of overheads, it isn’t good commercial sense to make new antibiotics that will sit on the shelf and only get used as a last resort. So the mantel is passed to smaller companies, academics and biotech companies.
This broken economic model has been recognised around the world, and in June 2020 the UK Government began a trial of an advance payment Netflix-style 'subscription' model to pay for antibiotics, where companies will receive a payment to develop new antibiotics, rather than payment for the number of their drugs used after they've been licenced.
Making a medicine – bridging the gap!
Before a drug can be licenced (sometimes called receiving marketing authority) the company or organisation developing it need to demonstrate to the satisfaction of the regulators that the drug does what they say it does, that it is safe and that they are aware of any possible side effects. There are also many other elements that will be scrutinised which need time and expertise to resolve.
Bigger pharmaceutical companies, working on multiple drugs for different conditions at the same time, have economies of scale to prepare for this scrutiny. However, for smaller biotechs, pharmaceutical companies and academic partnerships, this know-how and expertise can delay or stop drug development altogether; as it becomes too time consuming and too expensive. Preparing for this regulatory scrutiny is sometimes referred to as ‘bridging the translational gap’.
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What is CF?
Cystic fibrosis, or CF, affects the lungs, digestive system and other organs, and there are over 10,600 people living with it in the UK.
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