London Press Service Informs

DRUG BREAKTHROUGH CAUSES CANCER “CELL SUICIDE”

Outstanding medical research is well on the way to develop a new treatment for cancer that stimulates “cell suicide” and prevents the growth of blood vessels within tumours but has very little toxic effect towards healthy tissue in patients.
Called rimcazole, the treatment represents a highly attractive drug-development candidate because it has already been the subject of a clinical trial programme in a different therapeutic area, in schizophrenia. Now, the University of Dundee in Scotland and drug development company Modern Biosciences are to develop rimcazole together.
The re-profiling of rimcazole for cancer is at lower risk than a normal development programme because there is already a considerable amount of pre-clinical and clinical safety data available. This will allow Modern Biosciences to move into phase-1 trials rapidly.
The development of rimcazole for the treatment of cancer has been made possible through the groundbreaking research of Dr. Barbara Spruce and her team at the university. Dr. Spruce’s work has focused on the sigma-1 receptor, the subject of considerable pharmaceutical research in the field of psychiatric and neurological disorders.
She and her team were the first to show that agents (such as rimcazole) that bind to the sigma-1 receptor cause tumour cells – but not normal cells – to undergo “cell suicide”.
Dr. Spruce, senior lecturer in the Department of Surgery & Molecular Oncology at Dundee University, said: “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 that rimcazole will produce good anti-tumour effects while, crucially, sparing healthy cells.”
She continued: “I would like to acknowledge the hard work and commitment of my team and the help of my many collaborators at the University of Dundee, including Dr. Neil Perkins and Dr. Alan Prescott; and also collaborators outside Dundee, in particular Dr. Suzanne Eccles at the Institute for Cancer Research at Sutton, Surrey [near London].”
In recognition of her work, Dr. Spruce received the inaugural Gannochy Trust Innovation Award of the Royal Society of Edinburgh in 2003.
Rimcazole has several features that make it particularly promising for the treatment of cancer; these are:
• 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 that are resistant to existing drugs;
• it has very little toxic effect towards normal, healthy tissues – meaning it is likely to have a low side-effect profile.

Cancer killer: groundbreaking research by Dr. Barbara Spruce (pictured) and her team at Dundee University, UK, has led to the development of rimcazole to treat cancer. Their work shows that agents (such as rimcazole) cause tumour cells – but not normal cells – to undergo “cell suicide”.

Under the agreement, the university will grant an exclusive worldwide licence to Modern Biosciences for the development of rimcazole in cancer. Modern Biosciences will fund and manage the development programme. Revenues generated through commercialisation of the drug will be shared by the university and Modern Biosciences that expects rimcazole to be in clinical trials in patients within a year.
The university, with the help of funding from the Wellcome Trust, the North-East Scotland Technology Fund (NESTech) and Scottish Enterprise, has progressed rimcazole to the point of clinical development, described as “a unique achievement within a Scottish university”, by experts.
Modern Biosciences plans to initiate phase-1 dosing studies in healthy volunteers this year. Phase-1 trials, which will monitor tumour growth and several biomarkers that are indicators of disease progression, are expected to start in 2008. The company believes that proof-of-concept data for rimcazole in cancer could be available within two years.
Dr. James Houston, director of Research & Innovation Services at Dundee University, said: “We are delighted to see rimcazole progressing towards clinical trials in cancer. The deal with Modern Biosciences represents the culmination of years of hard and innovating work from Dr. Spruce’s research group and the university which has developed the project to a point where it is ready for clinical trials.
“The decision to develop rimcazole to this stage is an unusual and bold move by an academic organisation. We are extremely grateful to the Wellcome Trust, NESTech and Scottish Enterprise for supporting Dr Spruce’s work and we are very pleased to be collaborating with Modern Biosciences and its team of drug-development experts,” he added.
Dr. Sam Williams, chief executive officer of Modern Biosciences, said: “The re-profiling of rimcazole is perfectly suited to Modern Biosciences’ model which aims to quickly generate proof-of-concept data in man as a means to substantially increasing the value of its projects.” (www.modernbiosciences.com)
Dr. Richard Seabrook, head of Business Development at the Wellcome Trust’s Technology Transfer Division, said: “This is a very good example of how excellent science, conducted in a university environment, can reveal a new therapeutic intervention for adoption by industry and is exactly the type of outcome the trust seeks from its translation award funding.”
Dundee University has powered its way to an internationally recognised position of excellence in life sciences and medical research with particular expertise in cancer, diabetes, cardiovascular and tropical diseases.
The university has both a 5* rated School of Medicine and College of Life Sciences, with research expanding from “the cell to the clinic to the community”, and has a larger medical research complex than the National Institute for Medical Research in London. The university has an excellent track record in attracting research income and commercialising research activity.
The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending about 500m pounds each year to support the brightest scientists with the best ideas (www.wellcome.ac.uk).