Stratified Medicine: Research
MRC/ABPI Inflammation and Immunity Initiative
The MRC’s Stratified Medicine Initiative has drawn on experience gained through investment in three pilot consortiaunder the MRC/ABPI Inflammation and Immunity Initiative:
- Chronic Obstructive Pulmonary Disease (COPD).
- Rheumatoid arthritis.
This initiative brought together industry and academic experts —covering basic, clinical and therapeutic development research—to develop disease-focused consortia addressing the challenges of disease stratification and biomarker identification.
COPDMAP is building a number of research questions around a group of COPD patients. The aim is to get a holistic view of disease progression — all studies will be conducted on the same patient samples and groups with full clinical histories and phenotypes. Data will be shared across all partners in real time. Key areas for research include understanding the patients more deeply, investigating the exacerbation of symptoms after infection, identifying new disease mechanisms and better understanding the muscle wasting associated with COPD.
The Rheumatoid Arthritis Consortium
This aims to investigate two aspects of the disease, the first through the TACERA study —aiming to finda cure for early rheumatoid arthritis — and the second via a longitudinal observational study. This will be coupled with the development of an “immune toolkit” to identify the immunological changes that occur as early disease develops into more chronic rheumatoid arthritis.
MRC APBI STratification and Extreme Response Mechanism IN Diabetes (MASTERMIND)
The mission of the MASTERMIND consortium is to establish a platform for a stratified approach to the treatment of type 2 diabetes. This will act as a springboard for future research and development by academia and industry.
Stratified Medicine Consortia Awards
The initiative’s first awards, totalling c. £25 million, were made to six consortia targeting:
- Rheumatoid arthritis (funded in collaboration with Arthritis Research UK).
- Hepatitis C.
- A rare genetic condition called Gaucher’s disease.
- The liver disorder primary biliary cirrhosis.
Supported in partnership with Arthritis Research UK, the MATURA consortium, led by Queen Mary, University of London, and the University of Manchester, aims to enable early, effective treatment and improve the cost-effectiveness of care for around 500,000 people in the UK who suffer from the painful inflammatory condition rheumatoid arthritis. It will search for biological and genetic markers in blood and joints which could be used as clues to predict how patients will respond to anti-inflammatory drugs. If successful it is estimated that a stratified treatment approach for this condition could save the NHS £13-18million a year. Co-funded by a £1million grant from Arthritis Research UK, this project combines 12 academic groups with nine industry partners.
A hepatitis C consortium led by the University of Oxford will develop cutting-edge gene sequencing technologies to find out why 30 per cent of people fail to respond to a new type of hepatitis treatment called direct antiviral therapy. The group of 14 academic institutions and eight industry partners will use a state-of-the-art clinical database and a bio-repository of blood samples from hepatitis C infected people. This has been established by Hepatitis C Virus(HCV) Research UK — a multi-disciplinary collaborative enterprise funded by a £1.92million grant from the Medical Research Foundation and based at the MRC-University of Glasgow Centre for Virus Research. This information will help the STOP-HCV consortium to decipher the genetic makeup of both the virus and the patient, drawing this information together to improve patient care.
The GAUCHERITE consortium
This aims to improve the care of people with Gaucher’s disease, a rare genetic disorder in which a build-up of fatty chemicals causes bleeding, painful skeletal complaints and swelling of some internal organs. Even identical twins differ markedly in disease severity, indicating that non-genetic components play a role in the condition. Five treatments are currently available, but patients could respond differently to drugs because of the complexity of the disease. GAUCHERITE will bring together specialist doctors and scientists led by Cambridge University, who will examine at least 85 per cent of all UK patients and ‘stratify’ them by the nature of their disease to allow better targeted therapy interventions. They will also work closely with major industrial partners and patient groups.
Primary Biliary Cirrhosis (PBC) is thought to affect 20,000 people in the UK – currently, around 30% of patients with this condition do not respond to the only drug treatments available and their only option is a transplant. The new UK-PBC consortium led by Newcastle University and funded by a c. £4.8m award from the MRC will recruit half of those affected in the UK, 10,000, at sites around the country. This new collaboration, between scientists, doctors and patient groups, will provide a better understanding of why some patients respond to treatment and some don’t; work with pharmaceutical companies to develop new drugs; and design a national protocol to streamline treatment across the UK. This will help ensure that, in future, patients receive the right type and level of treatment depending on the severity of their disease and individual biological make-up, and determine whether that should be at their GP or in a specialist centre.
People with schizophrenia suffer from a range of symptoms as well as 'negative symptoms' such as a lack of motivation and withdrawal from social contact. Currently, antipsychotic medication is the mainstay of treatment and all existing drugs are thought to work by reducing transmission of a brain chemical called dopamine. However, around a third of patients fail to improve on these medications. The STRATA consortium, led by Kings College London and funded by a c. £3.9m award from the MRC, aims to build on new evidence from brain imaging and genetics studies suggesting that those who do not respond may have a completely different neurochemical abnormality in their brains, involving a chemical called glutamate. STRATA aims to develop a method to predict, ultimately as early as first hospital admission, which patients will respond to standard dopamine drugs, and which people are instead more likely to respond to the new glutamate drugs currently under development.
Psoriasis is a common, chronic, potentially disfiguring disease that affects more than one million people in the UK. In the past 10 years there has been a dramatic improvement in clinical outcomes for patients with severe psoriasis, due to the introduction of a new class of injectable drugs called biologics. These work by targeting specific parts of the immune system which are important in causing psoriasis. However, these drugs are very expensive (estimated annual cost is £10,000 per patent) and it remains the case that a significant number of patients fail to respond adequately. The Psoriasis Stratification to Optimise Relevant Therapy (PSORT) consortium, led by the University of Manchester and funded by a c. £4.9m award from the MRC, aims to use existing knowledge about psoriasis, both clinical and scientific, and an unparalleled patient base, coupled to involvement of patient organisations and state-of-the-art investigative tools, to develop tests that can be used in the clinic to help direct personalised treatments.
Joint MRC and Technology Strategy Board (TSB) investments
In May 2011, the MRC and the TSB announced a joint investment of over £3.7m in seven major new company-led research projects aiming to place the UK at the forefront of developments into personalised medicine.
Four of the projects will look at biomarkers to predict how groups of patients respond to inflammation and immunological therapies. The other three projects will develop business models and value systems, and will try to determine the best ways to co-develop drugs and companion diagnostics, and the ways in which subsequent reimbursement can be distributed across the value chain.