Grant Awards News

In this new section we will be providing information about our latest grant awards.

Arthritis Research UK Microbiome Pathfinder Award.

New research led by Anne Barton, Professor of Rheumatology at The University Manchester, will investigate the role bacteria plays in the development and treatment of psoriatic arthritis (PsA), which could lead to tailored dietary and improved treatment.

Microbes live on our skin and in our guts and outnumber human cells by 10 to 1. They play a vital role in maintaining health and an active immune system. In recent years increasing evidence has emerged that microbes, including bacteria, contribute to disease development and how people respond to certain treatments.

Professor Barton, who is also Inflammatory Arthritis in Adult’s Theme Lead for the NIHR Manchester Musculoskeletal BRU, has been awarded £300,000 as part of the £1.5 million Arthritis Research UK microbiome pathfinder awards. Professor Barton’s research will explore the role of the microbiome in psoriatic arthritis (PsA), in collaboration with colleagues at The University of Glasgow.

PsA is a condition that causes painful inflammation in and around the joints and usually affects people who already have psoriasis. The team will analyse the bacterial groups from skin and stool samples of patients with PsA, before and after therapy, and investigate whether the composition of the bacteria correlates with the genetic make-up of patients,  the immune cells they carry and how they respond to treatment.

Most PsA patients have psoriasis before they develop PsA, meaning there is a window of opportunity to prevent them from getting arthritis. Understanding if certain bacterial communities are risk factors for PsA could lead the way to recommending dietary alterations, antibiotics and other lifestyle changes with the aim of preventing the onset of arthritis.

Professor Barton explained: “The microbiome is an unexplored link in the cause of arthritis; if an alteration in the skin or gut bacteria was identified that increased the risk of PsA, it is possible that topical treatments or dietary manipulation could be used to prevent arthritis in patients with psoriasis in the future.

“Furthermore, bacterial disturbances may affect the way medicines are absorbed. If this was known, for patients with PsA, current therapy options could be tailored according to the bacterial communities present or dietary manipulation could be used to change the composition.”

Researchers hope that by understanding which bacteria affect response particular treatments, they can develop better targeting of the right treatments to the right patients at the right time, within the next five-ten years.

http://www.arthritisresearchuk.org/research/news-for-researchers/2015/october/microbiome-research-awards.aspx

MAximizing Sle ThERapeutic PotentiaL by Application of Novel and Stratified approaches (MASTERPLANS).

MRC funding of £4.2m over 4 years for the 'MAximizing Sle ThERapeutic PotentiaL by Application of Novel and Systematic approaches' (MASTERPLANS) project. Funded under the MRC's second phase Stratified Medicine Initiative, Prof Ian Bruce will lead a consortium of 10 institutions and 11 industry partners who will aim to identify and apply in the clinic, factors that predict good response to therapy in patients with SLE. This will allow doctors to increase the early use of ‘most effective’ therapies.  This 'stratified' approach will also improve the success of future trials of new treatments for lupus which to date has had a disappointing record.

Lay Abstract: Systemic Lupus Erythematosus (SLE) is a chronic incurable disease caused by a person's immune system attacking organs and tissues such as the joints, skin, kidneys and brain. SLE affects one in 2000 individuals in the UK. Currently, treatment is selected based on a doctor's experience and on a 'trial and error' approach. Many agents take at least 6 months to show maximum improvement during which patients often require large steroid doses. It is recognised that long-term complications of lupus are associated with both ongoing 'grumbling' disease activity and chronic steroid use. Standard immunosuppressives such as mycophenolate mofetil (MMF) have had response rates of 50-60% in clinical trials and newer, more targeted’ biological therapies such as rituximab, belimumab and epratuzumab also report response rates in trials of 40-60%. Clinical experience and a number of studies have however suggested that there are certain patients who respond very well to particular treatments. The goals of a stratified approach therefore would be to allow doctors to maximise major response rates whilst avoiding / minimising chronic steroid therapy and aligning therapy selection better with our understanding of the key disease process in an individual patient. Our consortium will identify and apply in the clinic, factors that predict excellent response to therapy to allow doctors to increase the early use of ‘most effective’ therapies. This 'stratified' approach will also improve the success of future trials of new treatments for lupus which to date has had a suboptimal record.

To do this we will combine expertise from clinical and laboratory-based investigators, and link these with researchers working in the pharmaceutical industry. Our focus will be to identify factors that predict which patients do extremely well on any particular lupus treatment. We will start by focusing on a small number of drugs. As we demonstrate that this approach works well, we will be able to expand this method to other lupus treatments which are currently in development. We plan to re-analyse data already available from a number of large studies ongoing in the UK and internationally as well as to re-analyse data from previous lupus clinical trials. From these studies we will look for key predictive factors; such factors may include the type of lupus, genetic markers that the patient inherited and results of blood tests . In order to examine this question in even more detail, we plan to set up two parallel studies; one in patients with skin rashes due to lupus and one in patients with kidney involvement. In both these studies we will take biopsies to examine the affected tissue and also take blood and urine samples on a regular basis. These samples will be used to look in detail at how cells, proteins and other molecules change over time after a patient has been treated with a particular therapy. Combining this detailed information with the information gained from the larger studies we aim to better predict excellent levels of response to treatment.

This information will be used to help develop devices and/or computer programmes for the clinic to help find the most appropriate and effective treatment choices for patients with lupus. We plan to test our results in a clinical trial to examine whether this approach actually has more benefit for patients. Running alongside this, we will study the economic costs of lupus to the health care system as well as the costs of lupus to the individual and society. We anticipate that treating the right patient with the right drug at the right time will help control lupus better in individual patients, improve their survival rates and reduce their needs for need for steroid treatment. We also anticipate that this approach will significantly improve the quality of life of patients with lupus whilst also providing financial saving for the healthcare and benefits system.

http://blogs.mhs.manchester.ac.uk/news-hub/2015/01/29/manchester-to-lead-project-for-better-lupus-treatment/