PhD Thesis on Gaucher Research Completed


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Mary Teresa Moran presented a 310 page bound volume of her PhD thesis to Jeremy Manuel, Chairman of the Gauchers Association on 18 April 2000. The dissertation describes several genes that are overactive in the spleen and blood of sufferers of Gauchers disease which remain dormant in people without the condition. The discovery of one in particular opens up the possibility of treatment for bone disease for people with the condition. The Gauchers Association funded part of Ms Moran's three and a half year research project.


Dr Mary Teresa Moran's thesis entitled: Gauchers Disease: Differential Gene Expression in the Understanding of its Pathogenesis was recommended for the award of a PhD degree by the University of Cambridge in April 2000. It is the culmination of over three years hard work by Dr Moran which she has carried out in the Department of Medicine at Cambridge University since October 1996 under the supervision of Prof Timothy Cox and with the help of Dr Paul Schofield and other colleagues.

In her thesis Dr Moran says: 'Although mutations causing glucocerebrosidase deficiency clearly result in Gauchers disease, the link between the engorged macrophages (enlarged Gauchers cells) and the complex clinical phenotype (progression of the disease) remains obscure.'

Gaucher-specific Library

Dr Moran used a new technique to generate a Gaucher-specific library of genes which had previously been referred to. Out of 64 genes which Dr Moran extracted from the tissue of diseased spleens (taken from sufferers of Gauchers disease for clinical reasons and not for the purpose of this research), 17 genes were found to be overactive compared with those in spleens originating from individuals without Gauchers disease. Of these, the activity of three genes which produce cathepsins B, K, S were shown to be increased in the Gauchers spleens and they were also unexpectedly discovered to be significantly increased in the blood-stream of Gauchers patients. In particular, cathepsins B and K appeared to be related specifically to Gauchers disease activity.

The recent emergence of selective pharmaceutical inhibitors of Cathepsin K immediately opens up a possibility for a decisive clinical trial of their use in the bone lesions (abnormalities) that are so frequent in Gauchers patients,' writes Ms Moran in her final words of her thesis.

An article based on Dr Moran's thesis is accepted for publication later this year in the prestigious international haematology journal, Blood.

Mutual Support and Thanks

While thanking many people who helped her in her work, Dr Moran thanked members of the Gauchers Association: 'for your belief in the project, your continued support since starting my PhD and the opportunity to work on Gauchers disease'.

Mary Teresa Moran has helped us in a number of ways,' writes Jeremy Manuel. 'She has obviously carried out important fundamental research into the causes of Gauchers disease at a metabolic level and for that we are truly grateful.

She has also opened the way for our members and their friends to raise money to support research work such as hers which was a new venture at the time and I am thrilled to say everyone responded most generously.

And finally she offered to run in last year's London Marathon to raise money for the Association. Although unfortunately due to injuries she could not compete in the run, Les Bunyan stepped into her shoes and has now run twice for the Association. This year two other runners joined Les to complete the course. None of all this might have happened without the presence of MT (as her friends call her) in our midst.'


Article in the journal Blood
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Source: Gaucher's News August 2000.
© Copyright Gauchers Association 2000