Summary of the impact

Psoriasis is a chronic inflammatory skin disorder affecting up to 2.5% of the world's population, approximately 30% of whom eventually develop psoriatic arthritis, which can lead to debilitating long-term health problems. Current therapies are limited owing to side effects or reductions in efficacy. Prof Miles Houslay, University of Glasgow has performed internationally recognised research on drug targets to alleviate the symptoms of inflammatory skin conditions. Working with Celgene, Houslay identified lead compounds and assays to screen promising early compounds for the treatment of psoriasis and psoriatic arthritis for clinical development. This identified the lead compound (apremilast), which was subsequently developed by Celgene. Between 2010 and 2013, phase III trials on apremilast have validated it as a safe, clinically effective oral drug, on the basis of which apremilast was submitted for regulatory approval of its use in patients with psoriatic arthritis to the health authorities of the USA and Canada in March 2013.

Summary of the impact

Southampton research has been central to the development and international licensing of one of only two novel asthma therapies in the last 30 years, transforming asthma control and survival for severe allergic asthmatics.

Key studies by the Southampton Group have underpinned the development of immunoglobulin (Ig)-E as a key therapeutic target for controlling allergic asthma, with the Southampton-led first-in- man safety and efficacy trials critical to the registration of the anti-IgE therapy, omalizumab.

This contribution also generated significant inward investment in UK R&D and opened up wider investigation of anti-IgE therapy in a broad range of atopic and inflammatory indications.

Summary of the impact

Phosphodiesterase (PDE) research by Prof. David Adams of Heriot-Watt University (HWU) has discovered compounds with potent combined anti-inflammatory and bronchorelaxant activity, relevant to asthma and chronic obstructive pulmonary disease (COPD). This fuelled a major therapeutic development programme by the Japanese company, Kyorin Pharmaceutical Co. Ltd, resulting in 22 patents (18 published since 2008) with a direct link to the foundational work at HWU. The work was a key factor in Kyorin's continued commissioning of projects with Scottish Biomedical (SB) up to £14.9M, a technology management company founded by Scottish Universities, enabling SB's transition into a fully independent drug-discovery services company, [text removed for publication].

Summary of the impact

Phosphodiesterase (PDE) research by Prof. David Adams of Heriot-Watt University (HWU) has discovered compounds with potent combined anti-inflammatory and bronchorelaxant activity, relevant to asthma and chronic obstructive pulmonary disease (COPD). This fuelled a major therapeutic development programme by the Japanese company, Kyorin Pharmaceutical Co. Ltd, resulting in 22 patents (18 published since 2008) with a direct link to the foundational work at HWU. The work was a key factor in Kyorin's continued commissioning of projects with Scottish Biomedical (SB) up to £14.9M, a technology management company founded by Scottish Universities, enabling SB's transition into a fully independent drug-discovery services company, [text removed for publication].

Summary of the impact

Chronic, debilitating diseases such as arthritis, chronic obstructive pulmonary disease (COPD) and inflammatory bowel disease (IBD) could potentially be treated by damping down the underlying inflammation and therefore improving the quality of life of sufferers. Nrf2 is a protein that prevents inflammation when activated and many researchers have sought to manipulate its activity as a potential therapeutic strategy. However, this has had little success, due to a lack of suitable biochemical tools. We describe here the Nrf2-activating peptide TAT14, which was developed in Pharmacy and is now being marketed by biotech companies to study this important pathway.

Summary of the impact

Dalgleish proposed a programme to develop thalidomide analogues for their immunomodulatory and anti-neoplastic actions. Working with a small start-up company, Celgene, several analogues including lenalidomide and pomalidomide were developed and entered clinical trials. Both drugs significantly prolong patient survival in myeloma and myelodysplasia and have received FDA and NICE approval for these purposes. Celgene has grown into a large multi-national company with over 5000 employees. Lenalidomide sales were $3.8 billion in 2012.

Summary of the impact

King's College London (KCL) researchers were the first to identify that an early sign of diabetic kidney disease was the presence of albumin in the urine, a condition known as albuminuria. Building on this finding, the KCL Unit of Metabolic Medicine designed and led in-house, national then international randomised controlled clinical trials with the aim of preserving kidney function in diabetic patients. Ultimately, KCL research established that several drug inhibitors of the renin-angiotensin-aldosterone system (RAAS) can control albuminuria, slow the deterioration of kidney function and significantly extend survival rates in diabetic patients. These drugs are now generically available, and their prescription is recommended by current international clinical guidelines across North America, Europe, Australia and Asia. This shows major impact in terms of reach and significance.

Summary of the impact

Research undertaken within Imperial College showed that corticosteroid resistance in inflammatory diseases, such as chronic obstructive pulmonary disease (COPD) and severe asthma, is explained by reduced histone deacetylase-2 and that reversal of this resistance is possible with theophylline (in low clinical doses) and PI3Kδ inhibitors, which restore HDAC2 function. This led to the founding of a spin-out company RespiVert to develop potent inhaled inhibitors of PI3Kδ. The company has been very successful in finding such new molecules, which have proven to be safe in Phase I studies. RespiVert was acquired by Johnson & Johnson in 2010 and Phase II studies are now in progress in COPD and severe asthma.

Summary of the impact

The provision of effective and sustainable healthcare is a major challenge for society. In the developed world escalating costs are placing a huge burden on finite resources; in the developing world, where financial resources are often extremely limited, providing affordable healthcare is an even greater problem. One innovative route to help alleviate these problems is through drug redeployment, whereby existing drugs are employed in new ways to tackle serious diseases. Combining their knowledge of haematological disease gained from their research over the past 20 years together with a drug redeployment strategy, researchers in the School of Biosciences have developed and trialled new interventions for two blood cell cancers, Acute Myeloid Leukaemia (AML) and Burkitt's Lymphoma (BL), based on the administration of a combination of the lipid lowering drug Bezalip (Bez) and the female contraceptive Provera (MPA). As a result:

• Definitive significant outcomes have been demonstrated in terms of halting disease progression and / or diminishing disease load in patients suffering from AML and BL.
• Successful drug redeployment, on the basis of efficacy, absence of toxicity and low cost of drugs has been achieved.
• This intervention has created the means to reduce childhood mortality and improve the length and quality of life in areas of sub-Saharan Africa.

Summary of the impact

Sumbayev and colleagues have shown that gold nanoparticles represent an excellent platform for the specific delivery of drugs, targeting the HIF-1 biochemical pathway as a novel therapeutic target for diseases such as allergy, leukaemia and other autoimmune disorders. Two international, non-academic institutions have altered the direction of their work as a result of this research and two SMEs have revised their operational procedures and invested in the applied research that derives from this work.