Repurposing Disulfiram for treatment of 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, or abdominal cavity, 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, Pemetrexed and Cisplatin, 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.
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. We developed intraperitoneally injectable PLGA-encapsulated Disulfiram microparticles which is protected by recently-granted patents, for localized therapy of MM. Together with a collaborating team on the project -- Bank Valley Ltd, Pharmidex Pharmaceutical Services and the University of Wolverhampton -- Disulfican successfully completed the work on the initial stages of developing this new therapy for Mesothelioma treatment. Disulfican continues to carry out the necessary evaluation of safety, toxicity and efficacy so that clinical trials of encapsulated DS can be considered.