̽��ֱ�� of Cambridge - LifeArc

Rare disease research at Cambridge receives major boost with launch of two new centres

cjb250 — Mon, 22 Apr 2024 23:34:17 +0000

̽��ֱ��virtual centres, supported by the charity LifeArc, will focus on areas where there are significant unmet needs. They will tackle barriers that ordinarily prevent new tests and treatments reaching patients with rare diseases and speed up the delivery of rare disease treatment trials.

̽��ֱ��centres will bring together leading scientists and rare disease clinical specialists from across the UK for the first time, encouraging new collaborations across different research disciplines and providing improved access to facilities and training.

LifeArc Centre for Rare Mitochondrial Diseases

Professor Patrick Chinnery will lead the LifeArc Centre for Rare Mitochondrial Diseases, a national partnership with the Lily Foundation and Muscular Dystrophy UK, together with key partners at UCL, Newcastle ̽��ֱ�� and three other centres (Oxford, Birmingham and Manchester).

Mitochondrial diseases are genetic disorders affecting 1 in 5,000 people. They often cause progressive damage to the brain, eyes, muscles, heart and liver, leading to severe disability and a shorter life. There is currently have no cure for most conditions, however, new opportunities to treat mitochondrial diseases have been identified in the last five years, meaning that it’s a critical time for research development. ̽��ֱ��£7.5M centre will establish a national platform that will connect patient groups, knowledge and infrastructure in order to accelerate new treatments getting to clinical trial.

Professor Chinnery said: “ ̽��ֱ��new LifeArc centre unites scientific and clinical strengths from across the UK. For the first time we will form a single team, focussed on developing new treatments for mitochondrial diseases which currently have no cure.”

Adam Harraway has Mitochondrial Disease and says he lives in constant fear of what might go wrong next with his condition. “With rare diseases such as these, it can feel like the questions always outweigh the answers. ̽��ֱ��news of this investment from LifeArc fills me with hope for the future. To know that there are so many wonderful people and organisations working towards treatments and cures makes me feel seen and heard. It gives a voice to people who often have to suffer in silence, and I'm excited to see how this project can help Mito patients in the future."

LifeArc Centre for Rare Respiratory Diseases

Professor Stefan Marciniak will co-lead the LifeArc Centre for Rare Respiratory Diseases, a UK wide collaborative centre co-created in partnership with patients and charities. This Centre is a partnership between Universities and NHS Trusts across the UK, co-led by Edinburgh with Nottingham, Dundee, Cambridge, Southampton, ̽��ֱ�� College London and supported by six other centres (Belfast, Cardiff, Leeds, Leicester, Manchester and Royal Brompton).

For the first time ever, it will provide a single ‘go to’ centre that will connect children and adults with rare respiratory disease with clinical experts, researchers, investors and industry leaders across the UK. ̽��ֱ��£9.4M centre will create a UK-wide biobank of patient samples and models of disease that will allow researchers to advance pioneering therapies and engage with industry and regulatory partners to develop innovative human clinical studies.

Professor Marciniak said: “There are many rare lung diseases, and together those affected constitute a larger underserved group of patients. ̽��ֱ��National Translational Centre for Rare Respiratory Diseases brings together expertise from across the UK to find effective treatments and train the next generation of rare disease researchers.”

Former BBC News journalist and presenter, Philippa Thomas, has the rare incurable lung disease, Lymphangioleiomyomatosis (LAM). Her condition has stabilised but for many people, the disease can be severely life-limiting. Philippa said: “There is so little research funding for rare respiratory diseases, that getting treatment - let alone an accurate diagnosis - really does feel like a lottery. It is also terrifying being diagnosed with something your GP will never have heard of.”

Globally, there are more than 300 million people living with rare diseases. However, rare disease research can be fragmented. Researchers can lack access to specialist facilities, as well as advice on regulation, trial designs, preclinical regulatory requirements, and translational project management, which are vital in getting new innovations to patients.

Dr Catriona Crombie, Head of Rare Disease at LifeArc, says: “We’re extremely proud to be launching four new LifeArc Translational Centres for Rare Diseases. Each centre has been awarded funding because it holds real promise for delivering change for people living with rare diseases. These centres also have the potential to create a blueprint for accelerating improvements across other disease areas, including common diseases.”

Adapted from a press release from LifeArc

Cambridge researchers will play key roles in two new centres dedicated to developing improved tests, treatments and potentially cures for thousands of people living with rare medical conditions.

̽��ֱ��new LifeArc centre unites scientific and clinical strengths from across the UK

Patrick Chinnery

Alexander_Safonov (Getty)

Woman inhaling from a mask nebulizer

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Clinical trial underway to treat ultra-rare genetic disease with possible link to leader of mutiny on the Bounty

jg533 — Thu, 21 Mar 2024 09:00:00 +0000

A clinical trial to look at repurposing the UK-licensed medicine deferiprone for patients with the ultra-rare genetic disease neuroferritinopathy has launched today at the ̽��ֱ�� of Cambridge.

Neuroferritinopathy is a progressive and incurable brain disorder caused by changes in a gene that produces a specific protein - ferritin light chain protein. This change leads to the build-up of iron in the brain. ̽��ֱ��disease usually appears in middle-aged adults and causes severe symptoms that impact on day-to-day life, eventually resulting in the loss of speech and swallowing. There are currently no effective treatments.

Funded by LifeArc, the new randomised placebo-controlled trial - DefINe - will be led by Professor Patrick Chinnery from the Department of Clinical Neurosciences. It aims to stop the progression of the disease by reducing the iron accumulation in the brain with an existing drug called deferiprone. Deferiprone is an affordable oral tablet that is already licensed for use in the UK to reduce iron levels in blood conditions like thalassemia. If successful, the trial could also open the possibility of deferiprone being used for other neurodegenerative conditions linked with build-up of iron the brain.

Professor Chinnery said: “Neuroferritinopathy leads to severe disability and currently has no cure. ̽��ֱ��DefINe trial will show whether we can stop the disease in its tracks by pulling iron out of the brain using a well-known medicine called deferiprone.

“By funding this study, LifeArc has given the first hope of a treatment for affected families. If successful, the trial will open the possibility of using a similar approach for other neurodegenerative conditions linked to the build-up of iron in the brain, including Parkinson’s disease.”

Neuroferritinopathy affects approximately 100 patients worldwide. Initial discovery of the condition came when a surprising number of individuals diagnosed found to live in the Lake District in Cumbria experienced similar symptoms with a series of incorrect diagnoses. Research into the ancestry of these families by Professor John Burn, a clinical geneticist at Newcastle Hospitals NHS Foundation Trust, discovered the genetic commonality and also found an interesting potential link to the past.

Professor Burn found that a rare mutation caused the progression of the condition and almost all the known cases were likely to be descended from the same ancestor. He traced it back to the 18th Century in Cockermouth in Cumbria and families with the surname Fletcher. Professor Burn suggested they could have shared common ancestry with Fletcher Christian (Fletcher being his surname), known for leading the mutiny on the Bounty in April 1789, given he was also from the region.

̽��ֱ��DefINe trial will involve 40 patients taking the drug for a year, who will undergo state-of-the-art 7T magnetic resonance imaging (MRI) scanning to monitor the iron levels in the brain throughout. ̽��ֱ��evidence collected will form the basis of an application for licensing in the UK under ‘Exceptional Circumstances’, which is often used for rare conditions where the number of people affected is low. This means, if the trial is successful the drug could go on to benefit all people with the condition more quickly.

Samantha Denison, a patient hoping to participate in the trial, said: “It came as such a surprise to be informed of the trial and to learn that we have not been forgotten about. To have the chance to be involved in the trial gives me such hope. If it can help to slow or stop the condition progressing, that would be a huge relief. Just to know that by taking part we could also be helping future generations, is amazing.”

LifeArc has contributed £750,000 to the project and Lipomed, a Swiss life sciences company, has offered to provide both a cost-effective generic form of deferiprone, Deferiprone Lipomed, and a placebo to the trial – a Gift in Kind worth £250,000.

Dr Catriona Crombie, Head of LifeArc’s Rare Disease Translational Challenge, said: “Drug repurposing trials like this are an increasingly effective way of taking treatments that have already been approved and applying them to new conditions and diseases. This will help unlock new treatments for conditions that currently have few, if any, available."

Dr Chantal Manz, Chief Scientific Officer Lipomed AG, Switzerland, said: “Lipomed is very excited to support this promising study concept in patients with neuroferritinopathy, by providing deferiprone 500 mg film-coated tablets and matching placebo tablets. We recognise the unmet clinical need and the potentially significant benefit of this orally active iron chelator. Deferiprone is able to penetrate the blood-brain barrier and may reduce cerebral iron accumulation in patients with this extremely rare, but devastating genetic neurodegenerative disorder, for which no alternative treatments are available.”

Adapted from a press release by LifeArc.

If successful, the trial will open the possibility of using a similar approach for other neurodegenerative conditions linked to the build-up of iron in the brain, including Parkinson’s disease.

Patrick Chinnery

Patrick Chinnery looks at brain scans

Yes

Scientists identify 160 new drugs that could be repurposed against COVID-19

cjb250 — Wed, 30 Jun 2021 18:00:28 +0000

In a study published today in Science Advances, a team led by researchers at the ̽��ֱ�� of Cambridge’s Milner Therapeutics Institute and Gurdon Institute used a combination of computational biology and machine learning to create a comprehensive map of proteins that are involved in SARS-CoV-2 infection – from proteins that help the virus break into the host cell to those generated as a consequence of infection. By examining this network using artificial intelligence (AI) approaches, they were able to identify key proteins involved in infection as well as biological pathways that might be targeted by drugs.

To date, the majority of small molecule and antibody approaches for treating COVID-19 are drugs that are either currently the subject of clinical trials or have already been through clinical trials and been approved. Much of the focus has been on several key virus or host targets, or on pathways – such as inflammation – where a drug treatment could be used as an intervention.

̽��ֱ��team used computer modelling to carry out a ‘virtual screen’ of almost 2,000 approved drugs and identified 200 approved drugs that could be effective against COVID-19. Forty of these drugs have already entered clinical trials, which the researchers argue supports the approach they have taken.

When the researchers tested a subset of those drugs implicated in viral replication, they found that two in particular – an antimalarial drug and a type of medicine used to treat rheumatoid arthritis – were able to inhibit the virus, providing initial validation of their data-driven approach.

Professor Tony Kouzarides, Director of the Milner Therapeutics Institute, who led the study, said: “By looking across the board at the thousands of proteins that play some role in SARS-CoV-2 infection – whether actively or as a consequence of infections – we’ve been able to create a network uncovering the relationship between these proteins.

“We then used the latest machine learning and computer modelling techniques to identify 200 approved drugs that might help us treat COVID-19. Of these, 160 had not been linked to this infection before. This could give us many more weapons in our armoury to fight back against the virus.”

Using artificial neural network analysis, the team classified the drugs depending on the overarching role of their targets in SARS-CoV-2 infection: those that targeted viral replication and those that targeted the immune response. They then took a subset of those involved in viral replication and tested them using cell lines derived from humans and from non-human primates.

Of particular note were two drugs, sulfasalazine (used to treat conditions such as rheumatoid arthritis and Crohn’s disease) and proguanil (an antimalarial drug), which the team showed reduced SARS-CoV-2 viral replication in cells, raising the possibility of their potential use to prevent infection or to treat COVID-19.

Dr Namshik Han, Head of Computational Research and AI at the Milner Therapeutics Institute, added: “Our study has provided us with unexpected information about the mechanisms underlying COVID-19 and has provided us with some promising drugs that might be repurposed for either treating or preventing infection. While we took a data-driven approach – essentially allowing artificially intelligent algorithms to interrogate datasets – we then validated our findings in the laboratory, confirming the power of our approach.

“We hope this resource of potential drugs will accelerate the development of new drugs against COVID-19. We believe our approach will be useful for responding rapidly to new variants of SARS-CoV2 and other new pathogens that could drive future pandemics.”

̽��ֱ��research was funded by LifeArc, the LOEWE Center DRUID, the Bundesministerium für Bildung und Forschung, the European Union’s Horizon 2020 programme, Wellcome and Cancer Research UK.

Reference
Han, N, Hwang, W, Tzelepis, K, & Schmerer, P, et al. Identification of SARS-CoV-2 induced pathways reveal drug repurposing strategies. Sci Adv; 30 June 2021

Cambridge scientists have identified 200 approved drugs predicted to work against COVID-19 – of which only 40 are currently being tested in COVID-19 clinical trials.

We hope this resource of potential drugs will accelerate the development of new drugs against COVID-19. We believe our approach will be useful for responding rapidly to new variants of SARS-CoV2 and other new pathogens that could drive future pandemics

Namshik Han

geralt

Graphical representation of COVID-19 and networks

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Cambridge leads trial to see if tapeworm drug can boost protection from COVID-19 among vulnerable

cjb250 — Mon, 22 Mar 2021 08:16:58 +0000

If the trial is successful, it may pave the way for a new treatment to prevent or alleviate the impact of COVID-19 in people on dialysis, people who have had a kidney transplant, and people with auto-immune diseases affecting the kidneys such as vasculitis who require treatment to suppress their immune system. ̽��ֱ��treatment will last up to nine months.

Led by scientists from the Cambridge ̽��ֱ�� Hospitals NHS Trust and the ̽��ֱ�� of Cambridge, the PROphylaxis for vulnerable paTiEnts at risk of COVID-19 infecTion (PROTECT-V) trial will start in Cambridge with a plan to expand to other UK healthcare centres. It will recruit at least 1,500 kidney patients, who will be randomised to receive either a placebo (or dummy) drug, or UNI911 (niclosamide) as a nasal spray, both provided by the manufacturer UNION therapeutics, in addition to all their usual treatments. Participants can receive the vaccine and still take part in this trial, which will identify whether niclosamide can protect people from the virus either on its own, or in combination with any of the vaccines currently available.

Niclosamide has been re-formulated into a nasal spray so it can be delivered directly to the lining of the nasal cavity, like a hayfever spray. In the trial, people will take one puff up each nostril twice a day, as this is the part of the body where the virus can take hold. This ‘local’ drug delivery is likely to reduce the chances of people experiencing any side effects.

Usually used to treat intestinal worms and taken as a tablet, niclosamide has shown real promise in the lab. Early tests revealed niclosamide could stop SARS-CoV-2 multiplying and entering cells of the upper airways.

Dr Rona Smith, senior research associate at the ̽��ֱ�� of Cambridge and honorary consultant nephrologist at Addenbrooke’s Hospital, who is leading the UK study, said: “It is vital that we find a way to protect patients on haemodialysis and other high-risk kidney patients from catching SARS-CoV-2 and developing COVID-19. If they get it, they are more likely to fall seriously ill or die, and we need to find a way to change that.

“We believe testing niclosamide is particularly important for people who are immunosuppressed and have kidney disease, because their immune responses to vaccines can sometimes be less effective. While the vaccine will offer a level of protection, niclosamide may provide further protection against COVID-19 that doesn’t rely on the immune system mounting a response.

“If successful, our innovative trial could mean that the treatment becomes available to kidney patients more widely within months. It would mean they could receive their regular life-saving dialysis or take their immunosuppressant drugs without additional worry. And if it’s successful it could even be rolled out more widely – and benefit more vulnerable people.”

̽��ֱ��trial involves researchers and patients from across the UK. It is funded by LifeArc, Kidney Research UK, the Addenbrooke’s Charitable Trust and UNION therapeutics and is supported by the NIHR Cambridge Biomedical Research Centre. UNION therapeutics is supplying the drug.

Professor Jeremy Hughes, kidney doctor and chair of trustees at Kidney Research UK, said: “Sadly, one in five kidney patients receiving dialysis in hospital or who have a kidney transplant and tested positive for the virus died within four weeks. Many of those on dialysis are having to put themselves at risk and attend their renal unit for life-saving dialysis treatment several times each week. And those who have had a kidney transplant must continue taking their immunosuppressant drugs, despite these making them more susceptible to infection.”

“Repurposing already available drugs or those in the late stage of development offers the fastest route to bring benefit to patients at this critical time,” said Melanie Lee, CEO of LifeArc.

Announcing the PROTECT-V trial, Matt Hancock, Health and Social Care Secretary, said: “Since the beginning of the pandemic, we have worked to find the best treatments the world has to offer for COVID-19.

“We have been clear from the outset that it will be a combination of safe and effective vaccines, testing and therapeutics that will bring an end to this pandemic, and we will not rest until every individual in the country is protected against this awful disease.”

Kidney patients who would like to take part in the PROTECT-V trial should speak to their nephrologist in their local centre to find out if their centre is participating in the trial and if they are eligible to take part.

Adapted from a press release by Kidney Research UK.

UK researchers are launching a clinical trial to investigate if the drug niclosamide, usually used to treat tapeworms, can prevent COVID-19 infection in vulnerable, high risk kidney patients and reduce the number of people who become seriously ill or die from it.

It is vital that we find a way to protect patients on haemodialysis and other high-risk kidney patients from catching SARS-CoV-2 and developing COVID-19

Rona Smith

BarocoF

Coronavirus

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