Translational case studies
The abstract and additional information on the MRC awards will appear on the RCUK Gateway to research website in due course. Further information on the Innovate UK element of the scheme is available on the Innovate UK website.
Funding for Confidence in Concept - Success stories
The Confidence in Concept (CiC) scheme provides grants of between £250k and £1.2m to allow universities with promising basic research into new therapies, diagnostics and medical devices to move towards full translational development. The funding is used for viability testing, to build up sufficient data to attract more substantive funding; strategically addressing the need to bridge the valley of death. Institutions can use the funding to support a number of preliminary-stage projects, and are encouraged to partner with industry, where appropriate.
A fourth round of funding of £11.6m for 21 universities across the UK was announced on Monday 15 February 2016 by Universities and Science Minister Jo Johnson on a visit to the University of Birmingham. A full list of awards can also be found there.
Impact of the first three rounds
Over the previous three rounds of CiC funding the MRC has invested a total of £28M, which has already secured over £110M of further support from charities, the public sector and industry. The data generated has also supported the creation of 16 new spin out companies and led to the awarding of at least 27 patents.
University of Birmingham
In 2014 Professor Ann Logan and Professor Liam Grover from the University of Birmingham received £86,500 CiC funding for the development of a synthetic anti-scarring membrane dressing for corneal burns. The CiC funding allowed the team to continue work initially supported by BBSRC to apply the science to this important medical problem. Ann and her multi-disciplinary team have gone on to secure £2.3m funding from the MRC Development Pathway Funding Scheme to continue the development of the gel into an eye drop to treat corneal burns. Additionally, they have secured £1.6m funding from Wellcome Trust to develop the gel to treat cutaneous burns.
Professor Roy Bicknell and Dr Steven Lee also from the University of Birmingham received £127,333 from the 2014 round of CiC funding. The team used the award to study tumour samples and showed that many cancers displayed a protein call CLEC on their surface. They also showed they could engineer immune cells to target tumour cells that display CLEC.
Following this proof of principle study, the University agreed a formal collaboration with the Cell Therapy Catapult and Cancer Research Technology to develop a new immuno-oncology cellular therapy based on gene modifying T cells to target solid tumours. CiC has helped to translate this academic programme into a commercially viable cell therapy. The collaborating partners have launched a new company, Chimeric Therapeutics Ltd.
University of Edinburgh
Through the University of Edinburgh CiC in 2014, Dr Junichi Yamagishi secured £66k for a project to create personalised voices for patients with Motor Neurone Disease. Dr Yamagishi’s team, which included a programmer and a speech therapist developed a ‘voice cloning toolkit’ to enable non-IT expert speech therapists to build voices through repair and supplementation of patients voices with recordings from a donor voice bank. These are delivered from a simple iPad or laptop type device by manual touch or using eye tracking.
The validated concept went on to secure £127,000 from the MND Association to underpin the initial local commercialisation strategy. A more ‘user-centric’ approach was developed through winning £25,000 funding from the Digital Health Initiative (DHI) and progress is now being made towards further commercialisation
Imperial College London
Dr Michael Schneider of Imperial College London received CiC funding of £78,403 in 2013 for a project to identify small-molecule inhibitors of the pro-apoptotic signalling protein MAP4K4 (HGK), a therapeutic target in cardiac muscle cell death.
After hitting key research milestones the project received £2.7M Early Stage Seeding Drug Discovery funding from the Wellcome Trust for a multi-disciplinary collaboration with the Cambridge drug discovery firm Domainex. The foundations of this collaboration were laid through earlier CiC funding.
Queens University Belfast
The Queens University Belfast CiC fund enabled Dr Lorraine Martin and Professor Brian Walker to develop and clinically validate unique molecules called ProteaseTags™ with an award of £58,691. These ProteaseTags can selectively detect and bind to proteases including those which are disease biomarkers for respiratory disease.
In 2013 their research helped to establish ProAxsis Ltd, a company developing tests to enable patients to monitor their diseases at home. ProAxsis received £183,000 in additional funding from US-based charity the Cystic Fibrosis Foundation. In 2014 the company won a €50k Instrument award from the first round of EU Horizon 2020 funding for small businesses, the first company in Northern Ireland to do so.
The success of ProAxsis was covered in our 2014/15 Outputs Report.
University of Sheffied
The University of Sheffied’s Dr Vincent Cunliffe received an award of £39,918 to study zebrafish genetic models of epilepsy for antiepileptic drug discovery. A consortium of the University of Sheffield, the University of Liverpool, the University of Manchester and UCB Pharma in Belgium was created to establish and validate zebrafish genetic models of epilepsy and create and exploit a virtual pipeline for anti-epileptic drug discovery based on these zebrafish models. The project has led to two publications and a further substantive partnership with UCB Pharma. Nine novel zebrafish mutant alleles for a total of 5 different genes have been generated for future research. New data on the anti-convulsant properties of hits from zebrafish screens has begun to emerge and is likely to result in further industry collaboration opportunities.
Case studies – Vaccines and immunology
Project Title: Clinical assessment of a novel simian adenovirus-vectored influenza vaccine designed to induce broadly protective immunity
Universal flu vaccine that could protect against pandemic
Scientists at the University of Oxford have been awarded nearly £800,000 through the 1st round of the Biomedical Catalyst to test a universal flu jab that could protect against all known strains of the illness, including the more serious bird and swine flu. If successful, it could eventually replace the annual flu jabs offered to vulnerable groups (such as the elderly and pregnant women).
The vaccine, which has already been tested in a small number of healthy volunteers, works in a completely different way to traditional flu jabs. Instead of targeting the proteins on the outside of the virus, which vary from strain to strain, the new vaccine aims to target molecules inside the virus that are common to all strains. In doing so, it could provide rapid and broad immunity against flu infection and could also provide a booster for pre-existing immunity in adults and the elderly, which may have diminished over time.
The researchers will now test two variations of the vaccine in a clinical trial of healthy volunteers to find the best way of raising immune responses against the influenza virus. They will also test the vaccine in older people, whose immune systems often don’t work as well as younger people.
At the end of the trial they should have enough information to move into the later stages of clinical development, with the eventual aim of licensing the vaccine. The project builds on previous work from the Oxford research team, which was funded through the MRC Developmental Pathway Funding Scheme.
Project Title: Development of a Clostridium difficile Vaccine
A vaccine for hospital-acquired infection by Clostridium difficile
Researchers at Royal Holloway, University of London have been awarded £500,000 through Round 1 of the Biomedical Catalyst to develop a promising new vaccine for Clostridium difficile, a bacterial infection that kills around 3,000 people a year (almost four-times more than MRSA).
C. difficile bacteria are normally harmless in healthy people, but treatment with certain antibiotics can allow C. difficile to flourish in the gut leading to severe diarrhoea that can prove fatal. Infection is more common in the elderly and mainly occurs in a hospital setting.
Previous attempts to develop a vaccine have had limited success, but the Royal Holloway team has devised a new approach that targets a protein needed by the bacteria to colonise the intestine, preventing an infection from taking hold. Previous work suggests that this vaccine can protect not only against initial infection, but also relapse.
Furthermore, the vaccine could be given orally in a solution or tablet, making it straightforward to administer and without the need for injection. Using Biomedical Catalyst funding, the researchers will test the vaccine in mice and hamsters to identify the most effective dose and delivery mechanism, before moving into human trials. The scientists are partnered with pharmaceutical company GlaxoSmithKline, which has a long history in vaccine manufacture.
Case studies – Gene therapy and regenerative medicine
Project Title: Clinical trial of gene therapy for the treatment of achromatopsia
Restoring sight through gene therapy
Researchers at the UCL Institute of Ophthalmology have been awarded £2.1m through round 2 of the Biomedical Catalyst to conduct the first ever clinical trial of a gene therapy for cone cells, to treat a severe visual disorder called achromatopsia. If successful, the trial could not only lead to an effective new treatment for this condition, but also pave the way for gene therapy as a treatment for a wide range of sight problems.
Achromatopsia (ACHM) is a genetic retinal disorder that affects around one in 30,000 people. Sufferers are born unable to see properly in daylight and experience photophobia (discomfort or pain in bright light) and colour blindness.
In around half of cases, ACHM is caused by mutations in a single gene (CNGB3) resulting in the progressive loss of light-receptive cells of the retina called ‘cones’. There are currently no effective treatments for this condition.
In 2007, Professor Robin Ali and his team conducted the world’s first clinical trial of a gene therapy for retinal disease, treating 12 patients with a condition, called Leber's congenital amaurosis, in which children are born with no night vision. Their success in restoring some vision in these patients encouraged them to try a similar approach in other retinal conditions.
Gene therapy for achromatopsia
Professor Robin Ali and his team have developed a treatment that delivers a working copy of the CNGB3 gene into retinal cells to replace the defective copy. They have already shown that the treatment restores vision in mice, and with MRC funding through the Biomedical Catalyst they will now test this new therapy in a phase I/II clinical trial involving 12 patients.
The researchers will first test to make sure the therapy is safe, before following the patients for 12 months to assess whether it results in a substantial improvement in daylight vision. They will test first in adults, then in children to determine at what stage of the disease therapy is most effective. The project will run for five years in total, beginning in July 2013 with production of the viral vector to clinical standards.
Robin Ali, Professor of human molecular genetics at the Institute of Ophthalmology, UCL, said:
“The eye is a particularly good target for gene therapy because it is isolated from the body’s immune system, meaning the virus we use to carry the corrective gene will not be attacked before it reaches its destination. Given that the main improvement we are looking for is restoration of vision, we should also be able to tell fairly quickly whether the treatment has been successful, which is very exciting.
“When we tested this therapy in mice we achieved one of the most successful ever results in an animal model of retinal degeneration, which gives us great optimism in advance of our first human trials. If we’re successful, I’m confident this work will provide a springboard to develop further gene therapy approaches to give people back their sight.”
Project Title: RegenVOX: phase I/II clinical trial of stem cell based tissue engineered laryngeal implants
World’s first clinical trial of stem cell voice box
Professor Martin Birchall and colleagues at the UCL Ear Institute have been awarded £2.8m through the 2nd round of the Biomedical Catalyst to allow them to carry out the world’s first clinical trial of a stem cell based voice box transplant. The ultimate goal is to produce a safe and effective therapy suitable for routine NHS use, resulting in improved quality of life for patients and carers.
The larynx (voice box) protects the airway during swallowing, regulates breathing, and enables voice: all fundamental human functions. Over 2,000 UK patients a year lose laryngeal function due to trauma or cancer and 1,300 NHS patients a year have their larynx removed entirely.
Conventional treatments for these patients leave many with substantial problems talking, swallowing and breathing. For example, the use of combined chemotherapy and radiotherapy for laryngeal cancer results in hoarseness and painful swallowing and can even render the larynx completely disabled.
Being able to accurately replace the normal contours and structure of the larynx, for example by using a living tissue-engineered replacement, would transform the quality of life (and in some cases survival) of these patients.
In 2008, Professor Birchall co-led the pioneering research team which carried out the first transplant of a human windpipe (trachea) reconstructed using stem cells. Now, MRC Biomedical Catalyst funding is helping him to build on this success by developing the first clinical trials of a stem-cell-derived larynx transplant; a project known as RegenVOX.
The RegenVOX procedure involves preparing a reconstructed larynx, made from the patient’s own stem cells and a donor larynx. In the lab, the team uses chemicals to remove the cells from the donor larynx leaving behind a scaffold, onto which stem cells from the recipient can be grafted. This means that the finished implant will not get rejected, like normal transplants, so patients do not need to take immunosuppressant medication.
The team is also able to turn the patient's stem cells into cartilage-producing cells to give natural strength to the transplant, and into replacement mucous membrane cells to line the inside, just like a normal larynx.
The MRC previously funded the preclinical development of RegenVOX, and with this latest grant Professor Birchall hopes to carry out the first transplant procedures in around a year. The research team will then follow ten patients for two years to demonstrate that the procedure is safe and effective.
They will also evaluate the economics of moving treatments like this into routine healthcare, and determine the most cost-effective ways this can be managed, as well as ensuring the UK economy benefits from the potential value of this opportunity. The project will run for just over four years.
Professor Martin Birchall, Chair of Larynogology at the UCL Ear Institute, said:
“Losing the larynx can be devastating as it impacts on so many of the qualities that make us who we are. Patients not only lost their voice, but their breathing, swallowing, sense of smell, the ability to cough and even kiss are all affected. The possibility that we may soon be able to give these patients back their voice and vastly improve their quality of life is incredibly exciting. I’m very hopeful that our success in this field will lead the way for other, related, stem cell-based organ replacements in the future, such as for the oesophagus and even lung.”
Case studies – Psychology and mental health
Project Title: Active Assistance for Psychological Therapy (Actissist): Software to improve access and adherence to CBT targeting key relapse indicators in psychosis
Smartphone app to deliver CBT for psychosis
Scientists at the University of Manchester have received 3rd round Biomedical Catalyst funding to develop and test a smartphone app to deliver cognitive behavioural therapy (CBT) to people who have experienced a first episode of psychosis. If successful in patient trials, the Actissist app could help patients manage their condition more independently and prevent relapses of psychosis that often require unplanned admission to hospital. This would also lead to significant cost savings for the NHS.
Serious mental health problems such as schizophrenia affect 24 million people worldwide. Schizophrenia is the most serious form of psychosis – a general term that describes a change in people's behaviour, thinking and perception. Psychosis affects people's ability to socialise, work and carry out the tasks of daily life, and usually begins in early adulthood.
The first time someone experiences these changes is termed first episode psychosis. The period following this initial episode is critical in the long-term course of the illness because the majority of patients relapse, or experience more than one episode of psychosis. This makes the early phase of psychosis an important time to deliver treatment as delays in treatment can make problems worse.
There is evidence that a talking therapy called CBT can reduce the impact of psychosis. Unfortunately, only one in 10 of those who could benefit from CBT for psychosis have access to this treatment due to a shortage of trained staff and pressure on health service resources. Even when people are offered CBT, they often don't receive it until late in their illness, when it is less effective.
The Schizophrenia Commission Report (2012) found that early intervention services in psychosis have the potential to save the NHS £119m over three years.
Actissist – delivering CBT through a smartphone app
Researchers from the University of Manchester will use around £450,000 of Medical Research Council funding to develop and test an app to deliver CBT to patients in the early stages of psychosis.
The Active Assistance for Psychological Therapy (Actissist) app will allow patients to manage their own care at home through a familiar device (a smartphone). The app will deliver personalised CBT strategies that will allow patients to identify and manage their symptoms as part of their everyday lives, offsetting the potential need for unplanned hospital admissions, which can be highly distressing.
This proof-of-concept study will provide 24 first episode psychosis patients with a CBT smartphone app, and 12 people with an app designed to simply monitor psychosis symptoms. Which treatment people get will be randomly determined so that the effect of treatment can be compared in similar groups of people. If successful, the researchers hope the app could be further developed for psychosis and widened out to other mental health conditions.
This research will build on ClinTouch, another MRC-funded mobile phone app developed at Manchester, which monitors symptoms in severe mental illness. Actissist will extend the ClinTouch concept to provide treatment.
Dr Sandra Bucci, lead investigator of the study from the University of Manchester, said:
“Schizophrenia is a serious mental health problem and the onset of psychosis can be a frightening experience for people. The Actissist app has the potential to transform care for people who experience psychosis by empowering them to take ownership over their own care in the community.
“Our ultimate goal is to make helpful treatments more widely accessible and to provide more choice about how people receive treatment, with a view to reducing the number of psychotic episodes people experience, keeping people well and out of hospital. Currently 70 per cent of the costs of serious mental illness go on unplanned admissions to hospital, so reducing relapse will potentially lead to huge savings for the NHS.”
Project Title: Personalised monitoring and enhanced self-management in mental health (CareLoop)
A mobile app to help manage mental health in the community
A team of scientists at the University of Manchester has been awarded almost £900,000 of Biomedical Catalyst Round 1 funding to develop further a mobile phone app that helps patients with serious mental illness, such as schizophrenia and bipolar disorder, to manage their own condition and care more effectively at home.
Patients with serious mental illness can find it hard to manage their condition in a community setting and much of the NHS costs involved in caring for serious mental illness comes from unscheduled admissions to hospital when patients undergo relapse (a sudden worsening in their symptoms). Providing support to individuals so that they feel involved in their care is key to avoiding such relapse.
The ClinTouch app, developed using previous funding from the MRC Developmental Pathway Funding Scheme, is a personalised electronic tool that records information on an individual’s symptoms several times a day and uploads this data wirelessly to a database. This database allows a healthcare professional to keep an accurate record of the patient’s symptoms and any fluctuations that may indicate a deterioration in their condition.
ClinTouch has the potential to be as effective as monitoring patients through face-to-face interviews in the short term, and has been shown to be safe and acceptable. The researchers now plan to build an end-to-end system to allow long-term symptom monitoring, with a view to involving commercial and NHS partners.
Case studies – Small molecule
Project Title: Targeting the RA synovial fibroblast via cyclin dependent kinase inhibition - a phase IIa study
Repurposing a cancer drug to treat rheumatoid arthritis
Scientists at Newcastle University have been awarded £1m by the Medical Research Council in the 3rd round of the Biomedical Catalyst, for a clinical trial to see whether a drug developed to treat cancer can be ‘repurposed’ to treat rheumatoid arthritis (RA) in patients who do not respond to existing treatments.
The drug works by targeting a different type of cell from conventional therapies and could therefore succeed where conventional treatments have failed. The drug is being developed by Cyclacel Pharmaceuticals, a University of Dundee spin-out that has received two previous rounds of Biomedical Catalyst funding.
Rheumatoid arthritis is a condition in which the joints become inflamed and painful. It affects about one in every 100 UK adults and is thought to be caused by the patient's immune system mistakenly attacking their joints. The resulting inflammation is not only painful but reduces joint movement and eventually causes joint damage and deformity.
Most drugs currently used to treat RA work by reducing the inflammation in the joint, or by neutralising cells of the immune system and their products. Over the past 20 years, improved treatment strategies and better drugs mean that the outcome for RA patients has got better.
However, many patients still don't recover and about one in ten do not respond at all to conventional treatments. Scientists think that another type of cell – called fibroblasts – may be responsible for the arthritis symptoms in these patients; as well as limiting improvement in patients whose symptoms do respond to conventional treatments. In RA these cells divide uncontrollably and produce chemicals that eat into cartilage and bone and cause inflammation.
Using seliciclib to target fibroblasts
The Newcastle team, with collaborators at the Universities of Birmingham and Glasgow, will test a drug called seliciclib that they believe will reduce or stop abnormal fibroblast activity. Seliciclib works by blocking enzymes that are central to the control of the cell cycle, which stops fibroblast cells dividing. Seliciclib has been evaluated to date in approximately 380 cancer patients and is currently being tested in combination with another Cyclacel drug in cancer patients with solid tumours.
Researchers hope to show that the treatment is safe and potentially effective in RA. Initially they will treat patients who have had RA for at least a year and who are already taking treatment but not responding well enough. If this research is successful then they will test the treatment in RA patients taking different treatments, at different stages of their illness. The work will take place in Arthritis Research UK Experimental Arthritis Treatment Centres, which have been established in Newcastle, Birmingham and Glasgow.
Professor John Isaacs, Director of the Institute of Cellular Medicine at Newcastle University and lead investigator, said:
“Repurposing of drugs is a potentially powerful way of bridging the gap between early stage research and development of a new treatment. Compared with traditional drug discovery approaches, this is a considerably cheaper and quicker route to the clinic because it 'leap-frogs' the early stages of drug development. If our trial proves successful it could dramatically improve the treatment outcomes for RA patients. It could also lead to further repositioning of similar drugs to treat other diseases such as cirrhosis and lung fibrosis, which will deliver additional benefits for the health service and the UK life sciences industry.”