Translation Fund: projects we've funded
Non-blood contacting biventricular cardiac assist device that promotes heart restoration
CorInnova is a cardiac medical device company developing a non-blood contacting biventricular cardiac assist device for the treatment of end stage congestive heart failure that would potentially eliminate 40% of the adverse events associated with traditional left ventricular assist devices (LVADs).
Reducing adverse events would reduce healthcare costs and expand the eligible patient population in NYHA Class IV heart failure by 3 to 4 fold, resulting in a systolic heart failure device that could address the unmet medical needs of many of the estimated one million end-stage heart failure patients in the US and Europe.
The technology also has the potential to treat diastolic heart failure, for which there are no approved devices, and where pharmacological intervention has little success. Moreover, the device has the potential to promote cardiac restoration by promoting correct heart motion. CorInnova’s cardiac device has the potential to be approved by the NHS in the UK (unlike present LVADs) due to lower costs, making an end-stage heart failure treatment accessible to many needy patients in the UK.
The device is a direct cardiac compression device whose technology is a significant break with the prior art. CorInnova’s device is a collapsible thin-film inflatable “girdle” that surrounds both ventricles of the heart. Air inflates the device in synchrony with the heart and increases cardiac output by gently squeezing the heart with minimal air pressure. The Wellcome Trust funding is to test this technology, further develop this novel medtech device and complete a First-in-Human Study to Assess Device Safety and Hemodynamics.
Innovative water pumps enabling better healthcare
Thermofluidics has received a Translation Award to develop an innovative, low cost irrigation pump to improve the health of malnourished smallholders in the developing world. The solar powered water pump is based on entirely new technology with two components: the Non-Inertive Feedback Thermofluidic Engine (NIFTE) converts heat into fluid oscillations without moving parts and the Double Acting Hydraulic Ram (DAHR) uses fluid oscillations to generate shock waves that draw water from deep below ground and pressurise it at the surface.
The NIFTE/DAHR is easy to maintain and can be manufactured from inexpensive materials (aluminium and plastics) using low cost production methods (moulding and extrusion). It has numerous other health-related applications including water pumping for drinking and sanitation, solar hot water provision, refrigeration, and oxygen enrichment of air. Tom Smith and Mark Bryant will lead the project, which will involve conducting developing-world field trials under controlled-conditions followed by stand-alone field trials of prototypes leased to farmers on working farms managed by Thermofluidics’ partners in India and Kenya. The team’s aim is to conduct a pilot production-run and commercial launch at the end of the project.
The project builds on previous funding from the Trust to develop a functioning pump suitable for a smallholder delivering superior performance to a treadle pump. The current project will design and fabricate a modular set of parts from which prototypes will be assembled to cover a wide range of low-lift and high-lift scenarios from open wells and boreholes. The intention is that Thermofluidics’ pump will ultimately improve crop yields, income and health outcomes for up to 550 million malnourished smallholders across the developing world.
A bio-inspired artificial pancreas for the control of Type 1 Diabetes in the home
Type 1 diabetes is caused by the destruction of insulin-producing beta cells in the pancreas. Current management of type 1 diabetes can lead to prolonged episodes of high and low blood glucose which can have long term side effects such as blindness, kidney failure and heart disease.
The aim of this project is to develop an artificial pancreas for treatment of type 1 diabetes in the home environment able to manage variations in meal composition and external perturbations such as exercise, physiological stress and intercurrent illness.
A miniature microchip, which is capable of mimicking the behaviour of the endocrine pancreas, has been developed at Imperial College and this forms the basis of a bio-inspired artificial pancreas that automatically delivers hormones to control the blood glucose levels in response to changes detected by a glucose sensor. This project builds upon the existing development to create the first bio-inspired artificial pancreas capable of bi-hormonal glucose control to be used in a free-living environment. See also: http://www.imperial.ac.uk/bio-inspired-technology/research/metabolic/bionicpancreas/
Development of PeproStat, a new class of topical haemostat for the control of bleeding
Bleeding is a major cause of mortality during trauma and rapid control of bleeding is essential for safe and effective surgical procedures. Such bleeding is controlled by using “topical haemostats” that are applied directly onto the wound in the form of sprays, gels and pads.
The active ingredient in these products is often the enzyme thrombin that clots blood. These products have drawbacks related to the use of thrombin that limit their use, such as a slow onset of action as well as a lack of “ready-to-use” formulations. Thrombin is also sourced from donated blood, and therefore poses a theoretical contamination risk.
The company Haemostatix has developed a new class of peptide-based haemostat known as PeproStat to overcome the limitations of current haemostatic products. PeproStat controls bleeding by binding to the blood protein fibrinogen to rapidly form a clot. The company has been awarded funding from the Trust to test the product’s safety and effectiveness in a clinical trial.
A computer assisted system to reduce auditory hallucinations unresponsive to antipsychotic medication
About 25% of people with schizophrenia continue to suffer with persecutory auditory hallucinations despite drug treatment. Their capacity to work and make relationships is grossly impaired, often for the rest of their life.
Professor Julian Leff from University College London and colleagues at Speech, Hearing and Phonetics, UCL have developed and evaluated a novel therapy based on computer technology which enables each patient to create an avatar of the entity (human or non-human) that they believe is talking to them.
The therapist promotes a dialogue between the patient and the avatar in which the avatar progressively comes under the patient's control. This translation award aims to refine the system, streamline the technology to make it more user-friendly and evaluate the system by a randomised controlled trial conducted by an independent team of researchers at the Institute of Psychiatry, King's College London.
Total Shoulder Replacement System
Many people with arthritis of the shoulder would benefit from total shoulder replacement (TSR). However, the use of surgical implants is limited because the scapula has very little bone in which to fix the artificial joint. Additionally, access to the damaged joint and its proper visualisation are often difficult tasks for the surgeon, resulting in a high prevalence of implant misalignment that is exacerbated by uneven arthritic bone loss.The overall result can be premature TSR failure due to instability, loosening and accelerated wear.
Professor Andrew Amis and colleagues at Imperial College London are researching an innovative artificial shoulder joint which will be less destructive and yet more secure when implanted. It will use novel bearing materials to reduce wear rates. The component which fixes to the upper bone of the arm will feature a compact ceramic shell to allow its placement with minimal soft tissue damage. The project team is also developing a surgical guidance system to ensure accurate insertion and alignment of the prosthesis and a less-invasive surgical procedure that will negate the need for shoulder dislocation and thus enhance rehabilitation. The project will culminate in a pilot clinical study in patients.
Non-Invasive Blood Glucose Meters
Diabetes is affecting hundreds of millions of people worldwide who have to monitor their condition using invasive methods (e.g. pricking of finger or insertion of needle into hip region). It is clear that non-invasive, continuous monitoring has the potential to help and encourage patients to monitor their diabetes more closely due to the associated improved quality of life. This incentive will lead to a reduction of hyper/hypoglycaemic episodes and the subsequent reduction of long-term risks, such as morbidity and shorter life expectancy, when this condition is poorly monitored and managed.
The Trust has awarded a team, led by Professor Adrian Porch from University of Cardiff, £892k to develop a non-invasive blood glucose monitor (NIBGM). Their device will improve the quality of life of people with diabetes and, with better management of their condition encouraged by the device, improve their life expectancy.
It is fundamentally different from all other glucose monitoring systems on the market in that it does not require blood to be extracted from the patient, or for the sensing element to be inserted into the patient’s body. It is merely attached to the person’s hip with adhesive, does not require blood extraction, and provides an instant readout of the blood glucose level on a unit that can be carried in the person’s pocket. The underlying technology for the device is based on microwaves and how they interact with the person’s blood. However, there is no heating (the microwave field strength is much smaller than that generated by a mobile phone) and the only sensation is that of touch. It is envisaged that final device will be around the size of a £2 coin and will be ready for mass-manufacture.
Pravda (Proton Radiotherapy Verification and Dosimetry Applications) - Integrated computed tomography and dosimetry instrument for proton therapy
Radiotherapy is a fundamental weapon in the battle against cancer with some 40% of patients receiving it as part of their treatment. Standard x-ray therapy and proton beams work through selective cell destruction.
Proton therapy offers unique clinical advantages, because unlike x-rays, protons can be delivered precisely within the diseased tissue, leaving surrounding healthy tissue relatively unaffected. However, the tightly focused deposition of protons also creates potential risks, as errors in delivery of the treatment could result in high doses being deposited to healthy tissues.
To overcome this problem, Professor Nigel Allinson of the University of Lincoln has assembled a team of instrumentation scientists, medical physicists and oncologists to develop detectors that provide accurate information about the proton beam during treatment. The new detectors will also record individual proton tracks to allow full 3D images of the proton interactions with the tumour. This work will lead to more effective treatment of cancers both in children, who are at greater risk for developing secondary tumours from conventional radiotherapy, and in cases where tumours are located close to our vital organs.
Extending electropharyngeal stimulation for the improvement of swallowing function to chronically dysphagic stroke patients
Dysphagia - an inability to swallow food or drink - affects tens of thousands of stroke victims every year in the UK alone. It can lead to malnutrition but there is also a high risk of potentially lethal pneumonia as a result of inhaling solids, liquids or even the patient's own saliva. Sufferers are three times as likely to die within three years of a stroke than non-dysphagic stroke victims. There is no treatment: patients are 'managed' with puréed food, thickened liquids and in many cases are fed through a tube.
Addressing this problem has been the main research focus for over 15 years of Professor Shaheen Hamdy at the University of Manchester. Daniel Green of Phagenesis Ltd, is turning the results of his work into a practical treatment for dysphagia. The company's first product has already proven effective in treating patients in the few weeks after a stroke while the patient is still in hospital. Now, via a Wellcome Trust Translation Award, it is developing and testing a version of the device that is suitable for use with patients in the community who are living with dysphagia. The treatment principle is to apply an electrical pulse to the pharynx (the back of the throat) for ten minutes a day for three days. A benefit of this medical device is that it avoids many of the safety issues associated with surgery or long term implants.
Development of a novel bioartificial liver device for the treatment of patients with liver failure
In the UK, over 16,000 patients a year die of liver failure. Their livers have the capacity to repair and regenerate, but do not have time to do so. A device temporarily replacing liver function would save lives and reduce the necessity for liver transplantation worldwide.
Dr Clare Selden and her team at UCL have developed a prototype 'bio-artificial liver' (BAL) to address this unmet need. Its key element comprises functioning liver cells in an external bioreactor. Plasma from a patient with liver failure will be passed through the bioreactor, contacting the alginate encapsulated liver cells, so that the cells replace those functions that the sick liver cannot perform.
The machine will buy time for a patient's liver to improve or, if damage to the liver is irreversible, may buy time until liver transplantation can be arranged. The technology combines alginate encapsulation of a human liver cell line and subsequent culture of the encapsulated cells in a fluidised bed bioreactor - providing a convenient, manipulatable biomass in a form which maximises mass transfer between cells and perfusing plasma. The team have Translation Award funding to complete the design, specification, performance characterisation and manufacture of this fully biocompatible BAL.
Development of a novel artificial aortic valve for transcatheter implantation
Transcatheter aortic valve implantation (TAVI) allows delivering a valve substitute through the vascular system, avoiding the need of open heart surgery. TAVI represents an ideal answer to the need of the expanding aged patients’ population.
The objective of the project led by Dr Gaetano Burriesci at UCL is the manufacture and pre-clinical assessment of a novel prosthetic aortic valve suitable for TAVI. An original design and the use of a novel synthetic functional nanocomposite polymer should result in a device which has the advantages over existing valve replacement of being fully retrievable/repositionable, has enhanced anchoring and sealing, maximises expanded/collapsed diameters ratio and has an extended durability.
Development of TIPS microspheres for the treatment of fistulas
Perianal fistulas are abnormal channels formed between the anal canal and the skin surface. Existing treatments to close these channels typically involve medical and surgical approaches, however both have limitations.
Medical agents are usually delivered systematically, but this may predispose the patient to severe infection and autoimmune reactions. Surgery using existing anal fistula plugs is successful in the treatment of simple fistulas but is associated with a high failure rate in more complex fistulas and in patients with Crohn’s disease.
Dr Richard Day from University College London has received a Translation Award to develop a potential solution to this problem. He and his team have developed microspheres that, when packed into a fistula, provide a ’scaffold’ that cells can grow between and into. As the microspheres dissolve, they are replaced by new tissue to heal the fistula. With this award, Dr Day and his team aim to demonstrate that the microspheres are safe when implanted into perianal fistulas in humans.
Development and validation of a novel device for detailed visual field assessment
Children and adults who suffer from certain types of brain tumours or other acquired brain or eye disorders can have visual problems resulting from defects in their peripheral vision (visual field defects). In children these can only be approximately measured in the clinic setting and similarly some adults have difficulties with the usual testing machine.
Professor Robert Minns and colleagues at the University of Edinburgh have developed a new system to detect visual field defects by monitoring a child’s eye movements when he or she is sat in front of a TV screen. This translation award aims to further develop and validate the system to enable more detailed testing (threshold testing) which could be of benefit for adults, especially those with glaucoma. The system is patient friendly (child or adult), not at all threatening and does not involve any head or other restraints. All that is required is just a few minutes in front of a TV screen and this gives the doctor detailed information about the patient’s visual field.
A portable, low cost, electronic urine flow meter to assess Lower Urinary Tract Symptoms (LUTS)
Lower urinary tract symptoms (LUTS) such as frequency, urgency and weak flow are often seen as an inevitable consequence of male ageing. They are significantly troublesome for around 30 per cent of men older than 50 years old, amounting to 1.8 million people in the UK.
The recording of urinary habits using a voiding diary and measurement of urinary flow rate are key steps in clinical assessment of men with LUTS, and the results guide treatment. At present, voiding diaries are manually completed by the patient and the urine flow test is performed in a clinic giving only a single, potentially inaccurate reading.
Dr Michael Drinnan and colleagues at the Freeman Hospital in Newcastle have designed and built a simple electronic flow meter-diary, specifically intended for home use. It can measure urine flow and record the volume, time and duration of each void for up to two weeks. The team have received Translation Award funding to improve the design, durability and functionality of the device for prototype production, and then formally investigate its usefulness in the assessment pathway for men with LUTS.
A bio-inspired artificial pancreas for Type 1 diabetes
The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive management of type 1 diabetes reduced complications by 50-76 per cent compared with conventional therapy. This was achieved at the expense of increased hypoglycaemia, especially when HbA1c levels <7.5 per cent were achieved. A closed loop system provides the potential to improve HbA1c levels while avoiding hypoglycaemia.
Professor Christofer Toumazou and Dr Pantelis Georgiou at the Institute of Biomedical Engineering together with Professor Desmond Johnston and Dr Nick Oliver at the St Mary's Hospital of Imperial College London have received a Translation Award to develop a bio-inspired artificial pancreas that will be used for closed loop control of type 1 diabetes. They aim to develop and clinically trial a microchip that will be used in conjunction with clinically approved glucose sensors and pumps to control blood glucose. The overall system will replicate the concentrations between 4 and 8mm and will therefore be the world’s first bio-inspired artificial pancreas. A film of Dr Nick Oliver and Dr Pantelis Georgiou talking about the device is available to watch on the YouTube channel of Imperial College London.
New signal analysis tools for defibrillators and pulse oximeters
An award to allow the generation of software that extends the functionality of defibrillators and pulse oximeters. CardioDigital Limited, a spin-out company from Napier University, Edinburgh, was established by Professor Paul Addison and Drs Jamie Watson and Brendan McGuckin to harness the increased signal analysis capacity of an established engineering-based method to give real-time patient status information.
Aircraft Medical Limited
Airway management is the most challenging risk facing anaesthetists. Laryngoscopes are used to guide a tracheal tube into the larynx to maintain a patient's airway during anaesthesia. A difficult intubation can lead to severe trauma and in some cases, death.
Aircraft Medical Limited, established by Matt McGrath, was granted Translation Award funding to develop an innovative laryngoscope that offers a near-guaranteed view of the larynx through the integration of a miniature video camera into the device and a display screen on the handle.
A Phase IIa/IIb clinical trial to evaluate the therapeutic efficacy of ChAd63-KH vaccine in patients with persistent post kala-azar dermal leishmaniasis (PKDL)
Visceral leishmaniasis (or kala azar) is a chronic and life threatening parasitic disease caused by infection with Leishmania donovani and L. infantum. There are approximately 400,000 new cases each year, mainly in Sudan, South Sudan, India, Bangladesh, Ethiopia and Brazil, with a case fatality rate of ~10%.
Although a handful of drugs are available, efficacy varies geographically and emerging drug resistance is a major threat. In East Africa and South East Asia, the lack of complete efficacy of these drugs can also lead to patients developing a chronic and stigmatizing skin disease, called post kala azar dermal leishmaniasis (PKDL). The development of new preventative and/or therapeutic measures to combat this infection is therefore a major international research priority.
An international research team, led by Professor Paul Kaye at the University of York, has developed a new adenovirus-based vaccine for visceral leishmaniasis, which has shown efficacy in animal models and safety and immunogenicity in a human Phase I clinical trial. This new study will allow the team to evaluate the vaccine for safety and therapeutic efficacy in Sudanese patients with persistent PKDL.
The study will first identify a safe dose of the vaccine to use in adults and children with PKDL and then proceed to test whether a single dose therapeutic immunization can stimulate immune responses leading to clinical cure or reduction in symptoms. If successful, these clinical trials will determine whether therapeutic vaccination has the potential to be developed further, as an alternative treatment option for patients with PKDL and perhaps other forms of leishmaniasis.
Clinical development of a therapeutic vaccine for Tuberculosis
Tuberculosis (TB), once among the world's leading infectious killers, is making a deadly resurgence because several new drug resistant strains have emerged. Some of these strains, which have emerged in India, Russia, and South America, are untreatable with any known antibiotic or antibiotic combination.
The ease of global travel has increased the risk of TB exposure, and drug resistant TB has been named as an important global bio-threat. New drugs take years to develop, and the pace of drug discovery and development cannot keep pace with mutations of the TB bacillus.
The use of vaccines as therapy is a proven method used in allergy, infection, and cancer, but to be effective the vaccines must be carefully chosen for safety and potency. However, no such vaccine currently exists for TB. Dr Steven Reed and colleagues at the Infectious Disease Research Institute (IDRI) have developed a novel vaccine for the treatment of TB. They have received an award from the Wellcome Trust to fund a clinical trial of this advanced vaccine candidate in former TB patients, who are at higher than average risk to develop TB again, to prevent recurrent disease.
Scalable in vitro production of red cells for clinical transfusion
Creating the ability to manufacture cultured red blood cells (cRBC) from stem cell lines is an important step towards solving supply shortages and reducing the risks of mismatched blood and transfusion transmitted infection in many countries. There is also increasing evidence that red cells stored for longer periods may have harmful effects in ill patients.
cRBC are likely to contain a higher proportion of younger cells than standard donated red cell concentrates and may, therefore, provide clinical advantages by surviving longer and performing better. Over the past 4 years with the support of the Wellcome Trust, Professor Marc Turner (Scottish National Blood Transfusion Service) and team have established a clinical grade Good Manufacturing Practice protocol for using stem cell lines to manufacture red blood cells.
The team, including Dr Jo Mountford, Professor Lesley Forrestor, Dr Rob Thomas, Professor David Anstee and Cell Therapy Catapult will build on this work to address 3 key issues: (i) improve and perfect this protocol, (ii) expand the manufacturing capacity (iii) conduct preclinical assessment and gain regulatory approval for initial studies in human volunteers. This work will provide the basis to attract investment for the development of large-scale manufacturing capability and clinical studies. The first clinical and commercial target will be treatment of chronic transfusion-dependent beta thalassaemia, where the complications associated with regular transfusion of red cells cause significant premature death world-wide.
A bio-resorbable, load bearing, tissue regenerative meniscal cartilage implant
Damage to the meniscal cartilage can result in progressive degeneration of the knee joint, in some cases requiring total replacement of the knee joint with a metal and plastic implant.
The problem is compounded by the fact that the meniscal cartilage fails to heal naturally in around 95 per cent of cases, and standard clinical practise has been simply to remove the damaged part of the tissue. To protect the knee and preserve its long term functionality, an absorbable implant is required to take over the function of the damaged tissue in the short term while allowing the meniscal cartilage to heal properly in the long term.
Orthox Ltd. is licensed to develop a new material, trademarked 'Spidrex®' and based on a silk protein, which pilot studies suggest meets the requirements for a meniscal implant. Principal Investigator and CEO of Orthox, Nick Skaer, has been awarded a Translation Award to design, develop and evaluate a Spidrex® meniscal cartilage implant and demonstrate its efficacy in a human clinical trial.
Repair of torn meniscal cartilage using stem cell bandage integration technology
Torn meniscus in the knee is a common injury that causes severe pain and discomfort and can prevent the sufferer from engaging in sporting activities. The only available treatment for most such tears is to remove the damaged tissue (partial menisectomy). This will relieve the patient of pain but carries a high risk of osteoarthritis developing in the treated knee.
Professor Anthony Hollander from the University of Bristol has received a Translation Award to develop a stem cell therapy to treat torn meniscus. The 'cell bandage' therapy will include delivery of the patient's own bone-marrow-derived stem cells into the damaged tissue using a biomembrane. The Translation Award will enable Professor Hollander to undertake all the preliminary work necessary in order to progress to a clinical trial within two to three years. The therapy will be developed by a University of Bristol spin-out company, Azellon cell therapeutics.
In-vivo testing of a novel rapid response intravascular fibre optic oxygen tension sensor to detect Cyclical Atelectasis and direct ventilator therapy in Acute Respiratory Distress Syndrome
In the 'sick lung' which afflicts many critically ill patients on the Intensive Care Unit, air sacs (alveoli) can begin to collapse in expiration and snap open again in inspiration. This cycle repeats itself with every breath and is known as cyclical atelectasis.
Mechanical ventilation of the lungs exacerbates this process and can cause further mechanical lung damage, and this can induce an inflammatory reaction which affects and damages other body organs. The mortality from ARDS is 30-50%. It is well established that prevention of cyclical atelectasis, by manipulation of the way in which ventilation is delivered, is beneficial to patients. The problem is that clinicians have no reliable and direct means of knowing when the process is occurring or if it is responding to therapy.
Researchers in Oxford lead by Dr Andrew Farmery and Professor Clive Hahn believe that the presence of 'oxygen oscillations' (breath by breath variations in the pressure of oxygen) in arterial blood can be used to detect the occurrence of cyclical atelactasis in the lung. Clinicians may therefore potentially use such a signal to adjust the ventilator settings guided by the amplitude of the oscillations thus minimising the atelactasis and mitigating the cascade of deleterious effects. The research team will develop a rapid-response oxygen sensor that will measure these oxygen oscillations in real time.
Metabolite biomarker-based screening test to predict pre-eclampsia
Pre-eclampsia is a serious disorder of pregnancy, which affects approximately 3 per cent of pregnant women and is associated with significant maternal and perinatal morbidity and mortality.
Currently, there is no clinically useful screening method to accurately predict which mothers will develop pre-eclampsia. Consequently limited healthcare resources are thinly spread and cannot be directed towards monitoring those women at greatest risk. Moreover, currently available and emerging disease prevention strategies cannot be targeted to high-risk women most likely to benefit.
Dr Louise Kenny from University College Cork and Professor Phil Baker from the University of Manchester have received Translation Award support to identify biomarkers in the plasma of women who subsequently develop pre-eclampsia. They will then test the performance of these candidate biomarkers in a large cohort of pregnant women (n=3000) akin to the normal antenatal population and develop a diagnostic which can be used to test for pre-eclampsia in widespread screening.
Preclinical development of a novel diagnostic for glaucoma
Glaucoma is the major cause (15 per cent) of irreversible blindness worldwide. A recent UK report suggested 10 per cent earlier detection of glaucoma would save £1billion/year in treatment costs alone.
Professor Francesca Cordeiro and colleagues from the Institute of Ophthalmology at University College London, have been given Translation Award support to fund the preclinical development of their Detection of Apoptosing Retinal Cells (DARC) Technology. DARC is a novel technique that utilises the unique optical properties of the eye to allow direct visualisation of dying nerve cells. If successful, early diagnosis and treatment would mean that DARC will increase patient benefit and decrease burden of care costs.
Wolbachia-based control of virus transmission by the mosquito Aedes albopictus
The Aedes albopictus mosquito transmits disease to humans living in tropical regions, including the viruses that cause dengue and chikungunya. One hundred million dengue cases can occur annually, and chikungunya epidemics are rapidly increasing in range and frequency. New and effective control measures are urgently needed.
In the wild, Aedes albopictus mosquitoes naturally carry a bacterium called Wolbachia in the cells of certain body tissues. Professor Steven Sinkins at University of Glasgow has developed a new Aedes albopictus strain that carries the Wolbachia bacterium that lives naturally within fruit flies.
Under laboratory conditions, this new strain is unable to transmit either dengue or chikungunya viruses. When this strain mates with wild mosquitoes, none of the eggs hatch. This means that over time, the new strain could replace the wild population with one that is incapable of transmitting dengue and chikungunya to humans.
The five-year project will undertake field trials in Malaysia to try to demonstrate the safety and effectiveness of this strategy for reducing mosquito-borne disease.
Transforming tissue repair: ‘out-of-the-bag’ elastic meshes that accelerate wound repair
Professor Anthony Weiss, University of Sydney, and collaborator Dr Rob Daniels of Elastagen, are developing a novel product to repair full thickness skin wounds arising from injury, surgery or disease. The product being developed is a mesh produced from elastin, a protein naturally present in the skin as fibres which are responsible for the skin's elastic properties.
Elastin also plays an important role in the regeneration of skin tissue following injury. However, as we age our bodies lose the ability to produce sufficient elastin to support this repair process. Through this Wellcome Trust sponsored research and development program the elastin mesh product is being refined to optimise its physical and biological properties and its safety and efficacy will be evaluated in preclinical models.
Field trials of synthetic sandfly sex pheromone to reduce human visceral leishmaniasis transmission
Visceral leishmaniasis is a major vector-borne public and veterinary health problem with few options for sustainable control. A synthetic copy of the male sand fly vector pheromone has been developed demonstrating that it attracts blood-seeking transmitting female sand flies to lethal insecticide, indicating the lures potential as a product to be used in operational programs to reduce infection and transmission.
As part of the registration portfolio, a 24 month stratified cluster randomised control trial (SCRT), led by Gordon Hamilton (Keele University), is underway in Brazil to test the efficacy of the product to reduce infection incidence in the sole reservoir host (dogs). The Interim analysis (half-way point) of the SCRT to demonstrate product safety confirmed that the product is not inadvertently causing harm. On the contrary, the relative risk of canine infection is declining, to be confirmed by the statistically powered follow-up at 24 months.
These results imply that the SCRT should also impact on human infection. This proposals objective is to strengthen the product’s registration portfolio by linking canine and human infection outcomes. The aims are (i) to demonstrate the product’s efficacy against human exposure/infection, and (ii) to characterise the product’s properties in line with regulatory and product development requirements, for effective field deployment.
Construction and testing of a whole-cell arsenic biosensor with a simple visual readout for field use
Arsenicosis from chronic consumption of contaminated ground water affects virtually all organs and tissues where skin lesions, bronchitis, gastroenteritis and ultimately a range of cancers are typical pathologies. Although arsenic contamination of drinking water is a global problem, it most seriously affects on the order of 100 million people in some of the poorest regions on earth including India/West Bengal, Bangladesh and Nepal.
Prof James Ajioka's team at Cambridge University and Prof French at Edinburgh University are aiming to construct an inexpensive and reliable kit to assess arsenic contamination in drinking water in rural villages. Based on the observation that some bacteria detect arsenic, they will engineer an arsenic sensing device based on the Bacillus subtilis arsenic operon.
This biosensor will be combined with a reporter system based on the violacein operon, resulting in bacteria that would turn green when it detects very low, safe levels of arsenic in the drinking water, but if the arsenic contamination is at a dangerous level, it will turn violet. The transcriptional signal to drive the pigment device in the bacteria can be tuned to respond to arsenic levels within definition of WHO safe or dangerous levels. The kit will be based on a weakened strain of the harmless soil dwelling bacteria, B. subtilis, housed in a robust plastic container to further reduce any risk and for easy, environmentally friendly deactivation/disposal.
Automated synthesis of Molecularly Imprinted Polymers
Molecularly Imprinted Polymers (MIPs) can be broadly considered as man-made equivalents of natural antibodies and are an important research target due to their potential to replace antibodies in medical diagnostics, therapeutics and general sensor applications.
However, traditional methods of synthesis yield bulk products or particles which are not easily integrated into sensors, difficult to process and have a broad range of affinities towards the target compounds, i.e. a mixed population of high and low-affinity binding sites. These problems can be solved by synthesising soluble MIP particles in the presence of a solid phase containing the target compound which doubles as an affinity separation matrix.
This way high-affinity particles are retained on the solid support as they are synthesised, allowing for subsequent removal of monomers and at the same time selecting only the 'good' ones which have high affinity towards the target. The products of this process (MIP nanoparticles) have recognition properties comparable to that of natural antibodies, and the potential to be used for the same purposes.
Researchers from Cranfield University lead by Professor Sergey Piletsky are seeking to develop an automated reactor that combines the synthesis and purification of MIPS using a unique method developed at the University. Currently there is no device available on the market for the production of MIP nanoparticles in the quality and quantities required by industry. The main goal is to produce a working prototype synthesiser and optimise its operational parameters based on the process described above for demonstration of its functional properties and market potential.
Automated high-dimensional outcome prediction in stroke
Stroke is a significant cause of death and disability around the world yet patient outcomes are not improving as fast as those for similar conditions such as heart disease. A major cause is the difficulty in providing targeted care in a patient group with hugely diverse treatment needs.
Dr Parashkev Nachev of the UCL Institute of Neurology, London has been given a Translation Award to develop a system for predicting outcomes in order to provide advance information on the optimal treatment for each patient. The system uses automated brain image analysis with high-dimensional computer-aided inference and exploits the finely specialized anatomical architecture of the brain, capturing the relation between the pattern of brain damage and the outcome in the patient with high fidelity. The Translation Award to Dr Nachev will be used to develop the technology to the point of direct clinical application.
Development of a device for medicines authentication by quadrupole resonance methods
Counterfeit and substandard medicines constitute a serious threat to public health. The scale of the problem is already great – particularly in the developing world – and is still growing.
The Trust has awarded King’s College London, in collaboration with Lund University, Sweden, a Translation Award to turn its expertise in applying the radiofrequency spectroscopic technique Quadrupole Resonance (QR) to the examination of pharmaceutical formulations into a robust, economical and portable medicines authentication device.
The proposed device will be able to identify the active pharmaceutical ingredient present in a pharmaceutical formulation, quantify it, and provide additional information that can be compared with genuine, high-standard medicines from approved sources without the need to know what other components are present in the pill formulation. As QR is a radiofrequency technique, it can detect signals from target materials through multiple-layers of packaging, making the method non-invasive and non-destructive. This project will serve as a springboard to commercialising the KCL-Lund approach through licensing the technology to a commercial manufacturer or establishing a spin-out company.
Evaluation of candidate genomic regions to determine genetic predisposition in populations of Alzheimer's patients
Population Genetics Technologies Ltd (PopGenTech) have created an approach for cost-effectively screening relevant, inherited genetic information in a large population of individuals.
PopGenTech's tagging, combining, and then analysing samples of the population as a single mixture, not individually, make it faster, easier and cheaper to relate differences in DNA sequence between individuals to inherited differences in susceptibility to disease or response to drug therapy.
In this project, funded by the Wellcome Trust, PopGenTech will apply its proprietary technology to investigate genetic predisposition to Alzheimer's Disease (AD). PopGenTech will initially screen specific genes that were identified in recent large-scale genome-wide studies of common genetic variants by Cardiff University and its fellow collaborators. The studies will use DNA samples, carefully chosen by scientists led by Professor Julie Williams at the Cardiff University MRC Centre for Neuropsychiatric Genetics and Genomics, from populations of AD patients.
The work will focus on genetic regions that involve pathways believed to be involved in AD pathology. The results achieved will validate the PopGenTech methods while providing Cardiff University with information on previously undetected rare genetic variants. Such rare variants could not only suggest possible targets for the development of future therapies but they can also provide additional objective markers for diagnosing predisposition and, when appropriate, guiding treatment strategies.
Sterile insect technique to control the mosquitoes that spread dengue fever
Releasing sterile insects has been used as an effective control method against agricultural pests for over 50 years. But it has not been applied to mosquitoes because of the limitations of conventional sterilisation techniques, such as radiation.
A technique called RIDL, developed by Oxford based company Oxitec Ltd, uses advanced genetics to modify male insects to be 'sterile'. These mosquitoes, which do not bite or spread disease, are then released to mate with wild females. No viable offspring can result from these matings and as a result, the mosquito population is reduced below the threshold level that is required to transmit the disease. Oxitec has created RIDL strains of Aedes aegypti, the principal mosquito species responsible for spreading dengue fever. The lead strain - OX513A - has already been tested both in the laboratory and in contained field conditions.
There is currently neither medication nor vaccine for dengue fever. According to World Health Organisation estimates, there may be over 50 million dengue infections worldwide every year and the only way to prevent transmission is to combat disease-carrying mosquitoes. The Translation Award will be used to fund open field trials to demonstrate the potential of the RIDL strains to reduce the Aedes aegypti population to below the threshold level.
Evaluation and development of a novel binocular treatment: I-BiT(TM) to improve vision in children with amblyopia
Amblyopia (lazy eye) is abnormal visual development in the brain during childhood causing poor vision in one eye. Amblyopia affects 2-3 per cent of the population and leads to restrictions in employment and risks of blindness.
Conventional treatment involves patching the "good" eye for hours each day which is unpleasant for the child and which has a detrimental effect on their ability to use their eyes together. Eye patching treatment adversely affects the quality of a child's life and so poor compliance results in poor visual outcome. Overall results are mediocre.
The novel I-BiT(TM) system stimulates both eyes simultaneously, but sends more detailed input to the amblyopic eye. Preliminary studies show highly encouraging results with reduced treatment times. Mr Richard Gregson and colleagues at Nottingham University Hospitals have been given Translation Award funding to develop and evaluate a new I-BiT (TM) system using 100MHz shutter glasses technology and to develop unique software for use on the system. The system will then be validated in terms of software delivery and in a crossover study comparing patching treatment and I-BiT (TM).
High throughput micro arrays for discovery of polymers resistant to bacterial colonisation
Many hospital-acquired infections are associated with implanted medical devices and more than 80 per cent have been estimated to involve biofilms.
Biofilm colonization of implanted medical devices increases the failure rate of the prosthesis and enhances the risk of lethal sepsis, e.g. catheters, shunts, heart valves, corneal implants, prosthetic joints. Morgan Alexander, Martyn Davies and Paul Williams at the University of Nottingham, in collaboration with Robert Langer and Daniel Anderson at MIT, have received Translation Award support to use novel polymer array technology to rationally design polymers for anti-biofilm properties that can be readily incorporated into standard medical devices.
Aspartyl protease inhibitors as anti-malarials
Malaria is one of the world’s most devastating diseases, causing over 450,000 deaths each year. The current therapeutics that treat this disease are becoming less effective due to emerging resistance. Novel therapies to populate the antimalarial clinical portfolio are urgently required.
A collaboration between Dr David Olsen from Merck & Co. (known as MSD outside the USA and Canada) and Professor Alan Cowman from the Walter and Eliza Hall Institute (WEHI), has demonstrated that malaria aspartyl protease enzymes are an attractive drug target. The enzymes perform essential functions for survival in blood, sexual and liver stages of the parasite life cycle.
By screening aspartyl protease inhibitor libraries, the collaboration has identified novel drug-like hit compounds that are potently active against the malaria parasite. The proposed research aims to increase potency against the parasite while maintaining selectivity, ultimately progressing to a lead optimisation stage discovery programme.
Development of a novel small molecule based therapy for schizophrenia
Schizophrenia is a severe and chronic mental health disorder that affects more than 21 million people worldwide. The disease is characterized by profound disruptions in thinking, affecting language, perception, and the sense of self, that typically includes psychotic episodes. Antipsychotics are the mainstay therapy for the treatment of schizophrenia. However, significant unmet need remains due to the limited efficacy and serious side effects associated with current antipsychotic medications.
Karuna Pharmaceuticals is developing KarXT, a novel product candidate for the treatment of schizophrenia that selectively targets the muscarinic system. KarXT is composed of xanomeline, a novel clinical-stage muscarinic receptor agonist and trospium chloride, an FDA-approved and well-established muscarinic receptor antagonist. Studies have shown that trospium does not enter the central nervous system and therefore the company expects that trospium would not inhibit xanomeline’s binding to muscarinic receptors in the brain.
Xanomeline has demonstrated efficacy in reducing psychosis and improving cognition in placebo-controlled human trials in both Alzheimer's disease and schizophrenia but has side effects associated with binding muscarinic receptors outside the central nervous system, limiting its therapeutic utility. Karuna believes that the addition of trospium chloride may reduce the side effects typically seen with xanomeline alone. Karuna plans to conduct a safety proof of concept study in 2016 to demonstrate that trospium chloride can improve xanomeline's tolerability profile, followed by a Phase II efficacy study.
Development of UCCB01-144 as a new treatment for stroke
Ischemic stroke, caused by a blood clot (thrombus or embolus), is a leading cause of death and disability worldwide with very few treatment options currently available. The only approved treatment is thrombolysis by recombinant tissue plasminogen activator (rtPA) but less than 10% of patients receives this treatment due to time-restraints and contraindications.
Avilex pharma has developed UCCB01- 144, a neuro-protectant that has demonstrated great effect in preclinical studies of stroke. The Wellcome Trust and NovoSeeds have co-funded Avilex pharma to complete the preclinical development of UCCB01- 144 enabling future clinical studies that will hopefully lead to the approval of a novel treatment for stroke.
Development of a small molecule therapeutic for the orphan disease Creatine Transporter Deficiency
The Wellcome Trust has funded Lumos Pharma to conduct a preclinical and clinical development program to ensure safety and efficacy of its promising drug candidate for the treatment of Creatine Transporter Deficiency (CTD).
CTD is an inborn error of creatine metabolism and autism spectrum disorder. The primary clinical manifestations of the disease are moderate to severe intellectual disability, severe speech and language delay, seizures, and behaviors associated with autism. It is hoped that the drug candidate can allow the afflicted children to develop normally and lead normal lives.
Lumos will conduct the nonclinical toxicology and safety pharmacology studies required to open an IND and initiate clinical studies. If these studies are successful Lumos will conduct a Phase I study in healthy volunteers to assess safety and tolerability and to further characterize the PK profile of the compound. Secondly, Lumos will conduct a Phase IIa study in CTD patients to examine efficacy.
Chemokine-based microbicides: Bridging from a first-in-human study to a pathway to licence
HIV/AIDS is still a catastrophic public health problem. Recent estimates show 2.3 million new infections per year and 1.6 million deaths among the 35 million people living with the disease. The problem is 95%+ in the developing world: young people, especially women and girls, are particularly vulnerable. The highest risk in rich countries is from receptive anal intercourse, with both women and men involved.
Although HIV/AIDS has become a largely treatable condition in rich countries, serious long-term complications are now emerging: cardiac, metabolic, mental health, cancer-related, accelerated ageing. Prevention is therefore key. A working vaccine still seems years away but another strategy is the use of ‘microbicides’, anti-HIV compounds applied to the genital areas to prevent infection during sex.
One such substance is called 5P12-RANTES. It is among the most potent anti-HIV substances known, potentially safer than many alternatives, and much better at avoiding drug resistance. Thanks to previous support from the Trust, a means of manufacture has been found opening the way to cheap manufacture even in some developing countries. The proposed project by Professor Robin Offord and colleagues at the Mintaka Foundation will allow a potential major backer to trial it in rectal use; permit development of long-acting formulations for vaginal and rectal use; and further reduce production costs with a view to transferring manufacture to developing countries.
Hypoxic tumour radiosensitisation using a tunable, nitric-oxide-neutral oxygen-binding protein technology
Glioblastoma (GBM) is the most common and aggressive primary brain tumor with a median survival of 14 months. GBM is characterised by low oxygen levels (hypoxia) which is known to worsen the prognosis for patients. Radiotherapy (RT) and chemotherapy (CT) are each more effective aganist oxygenated cancer cells compared to oxygen-deficient cells, and hypoxic tumour ceels are also more prone to recruit new blood vessels and invade neighbouring tissues.
Omniox has identified a new approach to overcome hypoxia in GBM by delivering oxygen deep into the tumour. Omniox' therapeutic candidate, OMX-4.80, is an oxygen-binding protein engineered to penetrate into tumours and release oxygen upon reaching areas that are hypoxic.
Dr Stephen Cary from Omniox has received a Translation Award to test OMX-4.80 in patients to ensure it is safe, accumulates tumours, and reduces tumour hypoxia. Ultimately, the team is developing OMX-4.80 to restore oxyten to improve RT and CT efficacy and extend the lives of patients with GBM. If successful in GBM, OMX-4.80 is likely to benefit other cancer populations in the future.
Development of a novel multi-valent, targeted treatment for serious Escherichia coli and Klebsiella pneumoniae infections
Phico Therapeutics Ltd has developed a novel antibacterial platform technology, SASPject, which utilises an antibacterial protein, SASP, which disables all bacteria by inactivating their DNA; without active DNA, bacteria cannot survive or multiply. The SASPject technology couples SASP with nano-delivery vehicles (NDVs).
NDVs are made from bacterial viruses (viruses that attack only bacteria), and Phico uses NDVs to selectively deliver SASP to those bacteria which are causing an infection. The unique way in which SASP works, by inactivating bacterial DNA even if it mutates, means that resistance is very unlikely to develop: any potential resistance that the bacteria could develop to the NDV’s themselves is addressed during development. SASPject can potentially be used against any harmful bacteria but being able to target it to selected pathogens avoids damaging the normal human flora. Uniquely, SASP could help to prevent the further spread of existing antibiotic resistance.
In this project, led by Dr Heather Fairhead at Phico Therapeutics plans to utilise and extend the company’s knowledge, experience and innovative techniques to produce a SASPject product that can be used intravenously to treat serious infections due to the Gram negative bacteria, E. coli and K. pneumoniae, including those which are multi-drug resistant.
Phase I trial: t4 immunotherapy of squamous cell carcinoma of head and neck (SCCHN)
Head and neck cancer causes over 2,800 deaths in the UK each year. Unlike many other cancers, the primary cause of morbidity and mortality is locally advanced disease, rather than metastasis.
To address this, Dr John Maher from King’s College London has received a Translation Award to test a novel treatment called T4 immunotherapy. T4 immunotherapy is a novel cell therapy in which patient immune cells (T-cells) are modified using a safe virus to express two new fusion proteins and are then expanded in culture for 2 weeks.
The first fusion protein is a chimeric antigen receptor (CAR) that enables T-cells to recognize and kill tumour cells that express any of a range of ErbB receptor pairs. The second fusion protein facilitates the expansion process, rendering manufacture of cell products more robust.
To maximise effectiveness and minimise risk, T4 immunotherapy will be injected directly into the tumour at a single setting, under ultrasound guidance. The primary focus of the study is the assessment of safety of this approach but several secondary objectives will also be investigated, including a preliminary assessment of effectiveness.
Bispecific small molecule antibody conjugate for hormone-refractory recurrent prostate cancer
The Wellcome Trust has funded a research team at the California Institute for Biomedical Research (Calibr) lead by Dr Chanhyuk Kim to develop a novel immunotherapy to treat prostate cancer.
Prostate cancer is the second most common cancer in men and kills 250,000 men per year worldwide. There is currently no effective treatment for prostate cancer which has progressed to hormone-refractory prostate cancer (HRPC). Patients with HRPC on average only live 1-2 years before succumbing to the disease.
In a search for new treatments, the team at Calibr have created a drug that engages the patient’s immune system to seek and destroy prostate tumor cells. This technique is a promising alternative to chemotherapy. The properties of this novel protein conjugate enable it to efficiently target malignant HRPC cells and recruit a robust anti-tumor immune response. Preclinical research demonstrates that this therapy effectively eliminates tumor cells both in vitro and in mouse models.
The primary goal of the proposed research is to develop this technology through safety studies and initiate pilot scale manufacturing. This will enable preparation of an investigational new drug application and serve as a catalyst for an industry partnership to carry out a Phase I clinical trial, thereby offering this innovative new therapy to patients with HRPC.
A systematic programme to develop and evaluate the best candidate treatments for repositioning as therapies for Alzheimer’s Disease (SMART-AD)
This innovative programme will identify drug candidates for repositioning in Alzheimer’s Disease (AD). Professor Clive Ballard and colleagues at King's College London, will compare the transcriptional signature of AD with the signatures of up to 4000 drugs with established safety in man to identify 100 candidates with the most promising therapeutic potential.
State of the art gene profiling will be used to determine the ability of the candidates to modify the expression of disease-associated transcripts in hippocampal neurons, with the best 20 drugs going forward to test for biological efficacy in in-vitro assays for a wide-range of pathogenic mechanisms implicated in AD. The six agents with the most favourable impact will then be evaluated in the best rodent model of AD to obtain the proof-of-principle evidence that would support a clinical program.
Importantly assays used will measure a range of key pathological and behavioural outcomes, as well as determining the drugs impact on disease-associated transcriptional changes. Each stage will be overseen by an independent expert panel to ensure drug selection is rigorous and appropriate for AD. The overall aim of this programme of research is to identify the best candidate to be taken forward to clinical trial in people with AD.
Treatment of obesity with the pancreatic polypeptide analogue PP 1420
Obesity is a massive health problem worldwide. Currently, no medication is safe and effective. Imperial College have developed a new drug for obesity called PP 1420, which uses the body’s natural satiety system for controlling appetite.
It is given as an injection once a day and works by suppressing appetite. In a previous study, Imperial tested PP 1420 for the first time in healthy volunteers, and found that it was both safe and without side effects. The Wellcome Trust are now supporting a further study of PP 1420 to show that PP 1420 is able to reduce food intake and body weight when multiple doses are given. This study is led by Professor Sir Stephen Bloom.
Development of novel small molecules for the treatment of antibiotic resistant bacterial infections
Due to a dearth of new antibiotics in development, resistant bacteria are presenting a growing challenge to patients, physicians, and health organizations, resulting in higher patient morbidity and mortality as well as increased health system costs. For example, the alarming spread of newly emerging “CRE” (Carbapenem-Resistant Enterobacteriaceae) “super-bugs” threatens to become a global crisis.
With an investment of $8.9M from the Wellcome Trust Translation Fund, VenatoRx is developing new antibacterial therapeutic products to address multi-drug resistant gram negative bacteria, including resistant E. coli, K. pneumoniae, and P. aeruginosa, important causative agents for complicated urinary tract infections, complicated intra-abdominal infections and many types of serious pneumonia.
First in Human clinical trials for SMT19969: A novel antibiotic for the treatment of Clostridium difficile infection
Hospital acquired bacterial infections continue to be a significant burden to the healthcare system and to patient welfare due to ever increasing rates of antibiotic resistance and the rise in prevalence of emerging and hard to treat infections.
One of the most important of these, Clostridium difficile, is a typically harmless bacteria that under certain conditions can cause a life-threatening infection of the colon. In particular, C. difficile infection (CDI) is associated with antibiotic use, which can cause an imbalance in the healthy bacterial population of the gut resulting in an overgrowth of C. difficile. There are estimated to be around 900,000 cases of CDI each year across North America and the EU and the infection now accounts for >80% of deaths due to gastroenteritis. Of particular concern are outbreaks due to hyper-virulent strains of the bacteria that are responsible for more severe forms of the disease.
Antibiotic choices for CDI are limited and of sub-optimal efficacy with up to 30 per cent of patients suffering at least one recurrence of the infection. Each recurrence tends to be more severe and is associated with increased risk of further infection. Combatting recurrent disease remains the central issue in achieving effective therapy for this life threatening infection.
SMT19969 is a novel antibiotic being developed by Summit Corporation PLC for the specific treatment of CDI. SMT19969 shows high levels of selectivity for C. difficile whilst having minimal effect on the normal healthy gut bacteria, which is expected to result in a significant healthcare benefit by reducing rates of recurrent disease. Preclinical development was funded by a Wellcome Trust Seeding Drug Discovery award. With continuing support via a Translation Award to Summit Corporation PLC the company is now undertaking Phase I first-in-man safety studies and Phase II efficacy trials.
Phase I dose escalation trial of a group B oncolytic adenovirus (ColoAd1) administered by intrahepatic artery infusion in patients with primary or secondary liver cancer
The Wellcome Trust has awarded up to £1.8 million to PsiOxus Therapeutics to support clinical development of a virus that attacks cancer cells. Clinical trials of the virus in patients are expected to begin in early 2012. Viruses that preferentially attack cancer cells whilst leaving normal tissues unharmed are known as oncolytic viruses.
The oncolytic virus ColoAd1 was developed using the evolutionary principle of natural selection to generate a virus with preferred specificity for cancer cells as a possible new therapy for cancer. Laboratory studies have shown that ColoAd1 has selectivity for killing cancer cells from a wide range of solid tumour types but shows little or no activity on normal tissue. Compared to other oncolytic viruses in development as cancer therapies, ColoAd1 has been shown to retain a high level of activity in human blood. This means that it could potentially be administered systemically as a treatment for cancer that has already spread to other tissues, known as metastatic disease.
PsiOxus will use the Translation Award from the Wellcome Trust to conduct a phase I/II clinical trial of ColoAd1 in patients with metastatic colorectal cancer, to determine the safety and tolerability of the virus. Future studies are also planned in patients with other solid tumour types, including primary hepatocellular cancer and ovarian cancer.
Development of a multi-peptide immunotherapeutic for Type 1 diabetes to first-in-human stage (MultipPepT1De)
Type 1 diabetes (T1D) is an inflammatory disease in which cells making insulin (β-cells) are killed by the immune system. It arises predominantly in childhood, is increasing in incidence and carries significant risk of disease complications and early death, even when patients have repeated daily insulin injections. There is thus an imperative to find well tolerated strategies for treatment and or prevention of T1D.
Professor Mark Peakman at King's College London School of Medicine has been awarded funding to develop a strategy known as peptide immunotherapy. By introducing selected fragments of key proteins from β-cells in a form that switches off inflammation, it is hoped that this therapy will "re-set" the immune system. Peptide immunotherapy is under development in other inflammatory diseases (allergy, multiple sclerosis) using cocktails of peptides, and shows considerable promise, as well as an excellent safety profile and the potential for long-lasting effects.
cGMP Manufacture of T-cells for immunotherapy
Gregg Sando, Cellmedica has received translational funding to develop a cGMP procedure to isolate and prepare T-cells for anti-viral therapy. T-cell immunotherapy has been shown to effectively treat viral infections on patients undergoing immunosuppression therapy, for example following transplant operations. Clinical availability of T-cells has been restricted in part due to regulatory issues. This project sought to address the lack of a cGMP protocol for this approach, using established commercially available laboratory protocols and drawing together several clinical experts from across the UK.