By Alan Wilson

A DUNDEE University research team has made a potentially major medical breakthrough by discovering that a drug used in clinical trials for schizophrenia can tackle cancer.

The re-profiling of Rimcazole as an anti-cancer drug comes after research by a team led by Dr Barbara Spruce, and could bring the university millions of pounds. Their research showed Rimcazole helps the body to kill cancerous cells but not normal cells, with very low side-effects.

The university has entered into an agreement with London-based drug development company Modern Biosciences plc to develop the new treatment in Dundee. If successful, it could be very lucrative for the university.

The university, with funding from the Wellcome Trust, the North-East Scotland Technology Fund (NESTech) and Scottish Enterprise, has progressed the drug to the point of clinical development, a unique achievement in a Scottish university.

Under the agreement, the university will grant an exclusive worldwide licence to Modern Biosciences to develop Rimcazole and Modern Biosciences will fund and manage the development programme. Revenues generated through commercialisation of the drug will be shared by Modern Biosciences and the university, with clinical trials expected to start within a year.

Scientists say Rimcazole represents an attractive development candidate as it has already undergone a clinical trial programme in a different therapeutic area, schizophrenia. Its re-profiling for cancer is therefore lower-risk than a normal development programme as a great deal of pre-clinical and clinical safety data is available. This will allow Modern Biosciences to move into phase I trials rapidly.

Dr Barbara Spruce, senior lecturer at the department of surgery and molecular oncology, said, “If the clinical trials are successful, there is potential for a multi-million pound benefit to the university and the company.

“One of the major problems with cancerous cells is that their ability to commit the normal process of ‘cell suicide’ or ‘apoptosis’ is reduced. Apoptosis is a natural self-defence mechanism designed to rid the body of rogue or damaged cells.

“If apoptosis fails, flawed cells survive when they shouldn’t and this includes cancerous cells.

“Rimcazole appears to restore apoptosis to cancerous cells, causing them to self-destruct but without doing so in normal cells.

“Our results lead us to believe Rimcazole will produce good anti-tumour effects while, crucially, sparing healthy cells.

“I would like to acknowledge the hard work and commitment of my team and help of many collaborators at the university, including Dr Neil Perkins and Dr Alan Prescott, and also collaborators outside Dundee, in particular Dr Suzanne Eccles at the Institute for Cancer Research, Sutton, Surrey.”

The research has found that Rimcazole has several features that make it particularly promising for the treatment of cancer. These include that:

* it is a small-molecule drug that can be taken orally;

* it works via a dual-mechanism of action that makes it highly potent, stimulating apoptosis (cell ‘suicide’) and preventing angiogenesis (the growth of blood vessels) within tumours;

* it works against a broad range of cancer types, including those resistant to existing drugs; and

* it has very little toxic effect towards normal, healthy tissues, which means it is likely to have a low side effect profile.

Dr Spruce’s work has focused on the so-called “sigma-1 receptor”—the subject of considerable pharmaceutical research in the field of psychiatric and neurological disorders. The team was the first to show that agents that bind to the sigma-1 receptor (such as Rimcazole) cause tumour cells, but not normal cells, to undergo apoptosis.

In recognition of her work, Dr Spruce received the inaugural Gannochy Trust Innovation Award of the Royal Society of Edinburgh in 2003.

Modern Biosciences plans to initiate phase I dosing studies in healthy volunteers this year and believes proof-of-concept data for Rimcazole in cancer could be available within two years.

Dr Sam Williams, head of Modern Biosciences, said, “We are very excited to… start the clinical development of Rimcazole, which has great promise as a selective cancer agent with a benign side-effect profile. The re-profiling of Rimcazole is perfectly suited to our model, which aims to quickly generate proof-of-concept data in man as a means to substantially increasing the value of its projects.

“We are also delighted to be working with the university and Dr Spruce to capitalise on their ground-breaking research.”

Dr James Houston, the university’s director of research and innovation services, said, “We are delighted to see Rimcazole progressing towards clinical trials in cancer. The deal with Modern Biosciences is the culmination of years of hard and innovating work from Dr Spruce’s research group and the university.

“The decision to develop Rimcazole to this stage is an unusual and bold move by an academic organisation. We are grateful to The Wellcome Trust, NESTech and Scottish Enterprise for supporting Dr Spruce’s work and we are pleased to be collaborating with Modern Biosciences.”