Translational Development of a novel therapy for Malignant Mesothelioma

There are an estimated 2.5 million people living with cancer in the UK, projected to increase up to 4 million by 2030\. Treatments and the outcomes for many cancers have improved, but not for rare, aggressive cancers such as Malignant Mesothelioma (MM). MM is an incurable cancer of the lining of the lung and chest (pleura) or abdominal cavity (peritoneum), typically caused by exposure to asbestos fibres. Despite multimodal treatment (chemotherapy, radiotherapy and surgery), MM is regarded as a terminal condition with a median survival of just 14.8 months. Fewer than 5% of patients survive for 5 years or more, representing one of the worst survival rates among all cancers. Only 2 chemotherapy drugs are potentially applicable and patients normally develop resistance to them.

Over the last 10 years, a multidisciplinary scientific team led by Professor Weiguang Wang at the University of Wolverhampton have researched and demonstrated that Disulfiram (DS), a drug used routinely for the treatment of alcoholism in millions of patients over more than 60 years, has excellent activity against MM. Whilst DS works well in the laboratory, it has never proven satisfactory in clinical trials. This is mainly due to the extremely short half-life of DS in the bloodstream (< 4 min). Professor Wang has found a way of encapsulating the drug in PLGA polymeric micro particles that protects the DS from degradation in the body and controls its release. Promising research results have been achieved for the encapsulated drug when tested in mice with cancer. The aim of this project is to carry out the necessary evaluation of efficacy and mechanism of action so that the team can progress towards clinical trials.

The collaborating team on the project -- Disulfican, Pharmidex Pharmaceutical Services and the University of Wolverhampton -- have successfully worked together before, in the initial stages of developing this new therapy. Disulfican was created as a spin-out company from the University of Wolverhampton in 2018, owns the patents and other intellectual property related to encapsulated DS, and is now focussed on advancing this therapy into clinic.

The partners focussed on mesothelioma because this condition is an 'orphan disease', due to its rarity and the absence of any very effective treatments. The UK regulator MHRA gives assistance with fees and procedures for therapies to address designated orphan diseases which means that the costs and timescales to get the drug approved for patients is reduced.