University of Leicester eBulletin

Scientists Discover Possible New Treatment for Genetic Diseases

March 2003
No 82

Imperial College London and University of Leicester Press Release

Scientists from Imperial College London, the University of Leicester, and Hammersmith Hospital have found a way to stop certain types of genetic diseases from occurring by modifying the way DNA is turned into proteins. 

The research published in this month’s Proceedings of the National Academy of Science shows how the researchers have been able to restore proper expression of defective genes, and that this might potentially have a positive effect in genetic diseases such as spinal muscular atrophy. 

The research was carried out at Imperial College London and the University of Leicester as a collaboration between Professor Francesco Muntoni and Professor Ian Eperon. 
 
Professor Muntoni, from Imperial College London and the Hammersmith Hospital comments: “Many genetic diseases are caused by the mutation of just one or two of the 3.2 billion base pairs of DNA which comprise our genome. The technique we have developed with our colleagues at the University of Leicester allows us to correct genetic mutations which result in abnormal splicing, as it is the case for spinal muscular atrophy.” 

Splicing is part of the process by which genes are converted into proteins. Large chunks of useless and meaningless sequence have accumulated in the genes of higher organisations, and the mutation of just one or two of the 3.2 billion base pairs which make up our genome can interfere with splicing. 
 
To make proteins genes first need to be processed into RNA (ribonucleic acid). The information in the genes is broken up into islands of information called exons, which need to be stitched together, while the meaningless sequences are removed. If the sequence of an exon is changed, splicing can be disrupted, causing genetic mutations. 

The researchers were able to stick the right sequences back into the exon by using short pieces of RNA (oligos), which stick to the exon of interest and had been modified to recruit signals that influence splicing. Using this novel strategy the splicing reaction can be manipulated.

This treatment was tested on cells from a patient suffering from spinal muscular atrophy. By putting these oligos into the cells, much of the protein required for the splicing process could be produced, allowing normal development of the cells. 

Professor Ian Eperon from the University of Leicester adds: “Although oligos have previously been developed to block expression of genes, this research indicates that we can also use them to restore the proper expression of defective genes. As well as working in diseases with a clear genetic basis such as spinal muscular dystrophy, we are aware that other conditions such as inflammation or cancer involve changes in the splicing of normal genes and our method might allow us to reverse these and facilitate treatment of the illness.” 

Spinal muscular atrophy is a serious and common disease affecting 1 in 10,000 births, resulting in mortality in babies who have the more serious form. The disease is caused by a mutation in a gene called SMN1. About 1 in 50 people have the defective version of SMN1. 


CELL TREATMENT: Untreated cells from patient show no spots of SMN protein in the nucleus (top picture), but after treatment some of the cells now show the normal pattern of SMN expression (bottom picture). [blue: nuclei of cells, red: SMN protein, arrows: spots of SMN protein in nucleus]

Even though everyone carries a second copy of the SMN1 gene, SMN2, this does not compensate for the problem as a difference in a single base pair from SMN1 in just one exon prevents proper splicing. This novel method, that could have broad applications also in other disease, offers a new strategy to try to correct the defect that causes spinal muscular atrophy. 

For further information, please contact:
Tony Stephenson, Imperial College London Press Office, telephone +44 (0)20 7594 6712, mobile +44 (0)7753 739 766, email at.stephenson@imperial.ac.uk
 
Ather Mirza University of Leicester Press Office, telephone +44 (0)116 252 3335, mobile +44 (0)7711 927821, email pressoffice@le.ac.uk
 
Notes to editors: 

Bifunctional antisene oligonucleotides provide a trans-acting splicing enhancer that stimulates SMN2 gene expression in patient fibroblasts, Proceedings of National Academy of Science.

Consistently rated in the top three UK university institutions, Imperial College London is a world leading science-based university whose reputation for excellence in teaching and research attracts students (10,000) and staff (5,000) of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and management and delivers practical solutions that enhance the quality of life and the environment - underpinned by a dynamic enterprise culture. Website www.imperial.ac.uk

University of Leicester:

* Founded as a University College in 1921
* 40 academic departments and more than 60 specialist divisions
* More than 140 degree programmes and 100 postgraduate programmes
* Rated as a top 20 University by the Financial Times and the Sunday Times
* Rated among the top 10 for research and contract grant income per full time member of staff. Grant income for last year in excess of £46m 
* Rated among UK top 10 for lowest student drop-out rate
* Over 18,500 students, including largest number of taught postgraduate students in the UK
* Won Queen's Anniversary Prize for Higher and Further Education in 2002 for achievements in Genetics 
* Internationally renowned for the revolutionary discovery of DNA fingerprinting and for housing Europe's biggest academic centre for space research 
* Co-founder of the £52million National Space Centre
* Website http://www.le.ac.uk

[University Home] [Press and Publications] [University Index A-Z][University Search][University Help]
Information supplied by: Barbara Whiteman
Last updated: March 2003
University Administration Web Maintainer

This document has been approved by the head of department or section.