Manchester Molecular Pathology Innovation Centre (MMPathIC): bridging the gap between biomarker discovery and health and wealth

Stratified medicine (which is allied to personalised or precision medicine) is an approach to treating patients through categorising them into groups based on their risk of developing a particular disease, or how they are likely to respond a particular drug or therapy.

It is key that the correct tests and techniques are available which can put individuals into groups (stratify patients), depending on their exact disease type and likely response to particular treatments. One way in which this might be possible is by application of molecular pathology, a specific type of pathology ( which is the study of disease), focused on the diagnosis and repeated characterisation of disease through the examination of molecules within organs, tissues or bodily fluids, such as blood, urine or synovial fluid (the fluid found in joints).

The aim of the Manchester molecular pathology node (Manchester Molecular Pathology Innovation Centre- MMPathIC) is to create an environment which enables new tests, based on molecular pathology techniques, to be developed. These can then be used to stratify patients, to allow more accurate diagnosis or prediction of the best treatments to use. As we already have significant groups of patient samples from people who suffer from inflammatory disease (psoriasis, rheumatoid arthritis and lupus), we will focus on these diseases in the first instance. These diseases are also important as, between them, they affect a large part of our population, treatment can be expensive (and often doesn't work first time, meaning patients have to try a number of expensive drugs before getting any relief from their symptoms), and these diseases often severely affect a person's quality of life due to pain and discomfort. In addition, we are going to build upon the lessons already learned in this area from our established expertise in cancer molecular pathology, which is far further developed in the provision of targeted therapies.

We will look at samples from patients with these inflammatory diseases, using a new technique that supports the measurement of many proteins within a minimally invasive sample (such as blood, urine or tissue). This will allow differences between samples from, for example, healthy people and people with a specific disease, to be examined- differences in certain proteins may prove useful as biomarker tests which can be used to diagnose a disease. In addition, by examining the differences in the levels of particular marker proteins from patients who respond to a drug compared to those who don't respond, doctors will be able to identify which drug is the best treatment for specific patients. This will hopefully have economic benefit as drugs will not be used on patients who will receive no benefit from them, but MMPathIC will ensure there is economic benefit through undertaking health economic analysis of potential markers- this will also allow informed decisions to be made by NHS officials who have to make decisions about which tests are viable for introduction into the health service.

As we can measure these proteins, we also propose ensuring that this data is linked to genomic data (the blueprint for these building blocks that are proteins) and health records- this integration will be facilitated by MMPathIC's staff, which will include skilled information specialists who can make sense of the data produced and data which already exists (data mining).

In collaboration with industry (who have the expertise to commercialise new tests, and navigate the necessary regulatory hurdles), we aim to produce at least 6 new tests which are ready to be commercialised, or ready to be used in hospital pathology laboratories in the first 3 years of the grant

Our aim is to establish an infrastructure: promoting biomarker discovery; translation into molecular pathology tests; NHS dissemination; and commercialisation.
-Discovery builds on existing strengths in "omics" technologies (notably £13M MRC Clinical Proteomics Centre [MRC-CPC], North West Genomic Medicine Centre [NW-GenMed]); University of Manchester's (UoM) Health Economics/Biostatistics, UoM TextMining (NaCTeM); Farr Institute safe haven for data analysis; and MIMIT (Manchester Integrating Medicine and Innovative Technology)
-Translation exploits the molecular pathology expertise across Central Manchester Foundation Trust's (CMFT) extensive laboratories and UoM's Experimental Molecular Pathology.
-Dissemination utilises interlinked NW networks of pathology laboratories, facilitated by Greater Manchester Academic Health Sciences Network (GM-AHSN)
-Commercialisation will develop around the partners' intellectual property commercialisation agents (UMI3, Trustech); commercial partners; and through Innovate's UK Precision Medicine Catapult (IUK PM Catapult)
All activities benefit from Manchester Academic Health Sciences Centre's (MAHSC) £3bn healthcare economy; UoM health economists; involvement of NICE and patient groups; local educational resource; and links with other nodes.
Ultimately we will produce an infrastructure for developing biomarker-based molecular pathology tests for many diseases, but initially we concentrate on key inflammatory pathways for diagnosing, stratifying and assessing therapeutic response of patients within our 3 MRC Stratified Medicine Programmes (MRC-StratMedP: MATURA £5.7M, rheumatoid arthritis [RA]; MASTERPLANS £5.1M, lupus; PSORT £5M, psoriasis)
A major MMPathIC activity is developing generic pipelines encompassing discovery and translation to GCLP standards. This we will pursue in intellectual partnership and shared complimentary resources with colleagues in CRUK's Major Cancer Centre to optimise time and cost effectiveness

Patients- will benefit from improved diagnostics, and new clinical tests which can predict prognosis and likelihood of response to specific treatments. Patients will be more fully informed about their condition at an earlier stage, diagnosed more quickly and be offered treatment sooner that is appropriate for the precise molecular nature of their disease, reducing the likelihood of adverse drug reactions, side effects, and the need to try multiple therapies before disease control is achieved. Morbidity and mortality will be reduced, patient safety and outcomes will be improved, with resultant effects on quality of life, and work days lost to illness.
Commissioners and policy makers- will be able to make informed choices about the indications for new and existing therapies. Clinicians can make smarter decisions about disease management and courses of treatments.
NHS- will save money through a quicker route to diagnosis, a reduction in invasive diagnostic procedures, and improved pathology and laboratory medicine services. This will reduce the necessity of inappropriate or aggressive treatment, and in turn, the economic burden of disease on the health service
Industry- MMPathIC will provide a pipeline of biomarkers which will be of potential interest for companies working in the diagnostic field to develop further into useable, marketable tests. New diagnostics for common conditions which make it into routine service have potential to produce significant revenue. The pharmaceutical industry will benefit from being able to implement improved clinical trial performance based on improved classification of patients, thus improving statistical significance and the likelihood of success of targeted therapies. Additionally, the node will provide infrastructure (both physical facilities and intellectual expertise), which smaller commercial companies can access (eg GCLP facility for protein biomarkers, health economist support, amongst others) which they don't have the capacity to provide in-house. MMPathIC will allow access to a test-bed regionally via GM AHSN (a potential population of 3M), and nationally via the wider node network. This represents a significant opportunity for industry who wish to demonstrate clinical and commercial proof of concept, and access to biobanks, patient cohorts and electronic health records. These benefits have the potential to be synergistic- smaller biotech and diagnostic companies will benefit from increased use of molecular diagnostics, and the opportunities this will bring in terms of companion diagnostic development alongside pharma's targeted therapies. Likewise, MMPathIC industry partners, through Manchester hub and the network model proposed by linkage with other UK nodes, will foster new links with other businesses working in this sphere, and potentially act as expert suppliers and service providers to each other, and collaborate via risk-sharing agreements.
Charities- will benefit from MMPathIC results and outputs through being able to tailor their translational research programmes accordingly. Charity-funded projects will be able to access the facilities of the node, representing value for money and cost-sharing (rather than replicating or duplicating resources on individual projects).
Clinical scientists- will benefit through the increased capacity to undertake discovery biomarker projects (through CPC and other infrastructure encompassed within, or accessible via, the MMPathIC molecular pathology node), which involve the most appropriate expertise in terms of validation, verification and informatics, from the outset. The development of a Pathology Masters in Research, based on our successful intercalated BSc, will increase capacity and allow the embedding of molecular pathology approaches across the clinical specialities. This will be complemented, through GM AHSN, by an increased awareness of molecular pathology across the health service workforce, across clinical/ non-clinical roles