25 July 2006

`Fat Controller’ may hold the key to breakthrough treatments in cystic fibrosis & other diseases

Researchers at the University of Dundee, Scotland, have uncovered key links between Cystic Fibrosis and other diseases and conditions including cancer, diabetes and obesity, findings which could open the pathway to new areas of research into understanding and treatment.

Dr Anil Mehta, who has worked in Cystic Fibrosis research for 20 years, and heads the European Union-funded Cystic Fibrosis Database based at the University, led the research which centres on the role in the body of a newly discovered hybrid protein dubbed the cellular "fat controller."

Dr Mehta and his team have uncovered genetic pathways which lead through this fat controller and form links between Cystic Fibrosis and the other conditions.

"It has long been known that Cystic Fibrosis patients suffer significant variations in weight - they tend to be very thin and can suffer very fast weight loss when they fall ill - but we did not know why this was the case," said Dr Mehta, a Reader in Child Health in the Department of Maternal and Child Health Sciences at the University of Dundee.

"Similarly it has been known that CF patients suffer a higher rate of cancer than normal and again we did not know why. In equal measure, almost half of these patients develop an unusual form of diabetes.

"What our research has uncovered are the genetic links, through this cellular fat controller, which we believe lead to these differences in fat metabolism and cancer. Furthermore, there are also significant links here to diabetes."

Dr Mehta said the findings could have a major impact on research into Cystic Fibrosis and the other conditions and, subsequently, the treatment of patients.

"The implications of this are that we have opened up a whole new area of research which links all of these conditions, and from here on in researchers looking at cancer, diabetes, obesity or Cystic Fibrosis should all be working with each other and looking at what the other is doing, because it is all linked together.

"We believe that these results could have a significant impact in terms of the treatment of patients with all three diseases - Cystic Fibrosis, some forms of childhood cancer and adult onset diabetes - and, hence, their potential life expectancy."

Dr Mehta’s research examined the relationship between three cancer-related enzymes that are associated with diabetes (NDPK), fat metabolism (AMPK) and Cystic Fibrosis (CFTR).

They found a new pathway between NDPK and AMPK which leads to variations in fat metabolism - this they have dubbed the "fat controller". Additional research found that these enzymes also bind to a protein that causes cystic fibrosis, CFTR.

The new research work was carried out by Dr Mehta and a team including Research Fellow Dr Russell Crawford. A team of international collaborators in Italy, Germany, France Portugal and the USA provided further support.

Results of the research, funded by grants from the Wellcome Trust and Cystic Fibrosis Trust over the last 10 years, are published in the scientific journals ‘Cellular and Molecular Biology’ and ‘Cellular Signalling’.

In order to further debate and create greater cross-disciplinary collaboration in this area of research, the University has agreed to support Dr Mehta’s efforts to host a major international conference of experts in NDPK, AMPK and CFTR in Dundee in September 2007.

NOTES TO EDITORS.

Cystic Fibrosis (CF) is an inherited disease that induces long term morbidity leading to multiple medical consultations. CF patients, in common with those with suffering from any other chronic disease, are widely dispersed throughout the United Kingdom. 5% of the population are carriers of the affected CF gene and there are over 1000 mutations producing clinical disease. The result is that the current 7500 or so patients in the UK present with a range of symptoms and degrees of severity of their condition, requiring therapies tailored to their specific needs.

The University of Dundee hosts the UK Cystic Fibrosis Database, which was started in Dundee in 1992 as a project to audit the health of CF patients in Scotland. In 1999, it was extended across the UK, and earlier this year plans were announced to extend the databse across Europe. Around 90% of CF sufferers in the UK - approximately 7000 people - are registered in the database.

The Wellcome Trust is the most diverse biomedical research charity in the world, spending about £450 million every year both in the UK and internationally to support and promote research that will improve the health of humans and animals. The Trust was established under the will of Sir Henry Wellcome, and is funded from a private endowment, which is managed with long-term stability and growth in mind.

The Cystic Fibrosis Trust is the UK's only national charity dedicated to all aspects of Cystic Fibrosis (CF). It funds research to treat and cure CF and aims to ensure appropriate clinical care and support for people with Cystic Fibrosis. For further information on CF and the trust, access their web page at: http://www.cftrust.org.uk/index.jsp

RESEARCH PAPERS

The full text of the paper in Molecular & Cellular Biology can be viewed at: http://mcb.asm.org/cgi/content/full/26/15/5921)

Details of the Cellular Signalling paper are at: http://www.sciencedirect.com/)

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