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Umeå researchers uncover new ALS gene

The ALS research team at Umeå University in Sweden, working with Dutch and Belgian colleagues, has found new connections between mutations in gene DPP6 and contracting the non-hereditary form of ALS. The findings are being published in this Sunday's edition of Nature Genetics on the Web.

To try to identify pathological genes that are involved in ALS, the research group at Umeå University, in collaboration with Dutch and Belgian scientists, compared DNA samples from 1,767 patients with non-familial ALS (so-called sporadic ALS, SALS) with DNA samples from 1,916 control individuals. This is the world's most comprehensive ALS study so far. They looked for DNA mutations that only exist in ALS patients, not in controls. After very extensive analyses they found that a DNA mutation in the gene DPP6 strongly correlates with SALS.

The DPP6 gene is on chromosome number 7 and codes for a protein enzyme, a peptidase that regulates the activity of so-called neuropeptides, that is, substances that affect nerve cells. DPP6 is therefore highly interesting as a candidate gene for ALS. Studies are now concentrating on finding disease-associated mutations in the gene. Just how mutations in the DPP6 gene can lead to ALS is unknown today. At present it is not possible to judge whether the discovery will lead to any new treatment for ALS.

The Swedish component of the study was carried out by Associate Professor Peter M. Andersen, molecular geneticist Anna Birve, and research engineer Ann-Charloth Nilsson, all with the Department of Pharmacology and Clinical Neuroscience, Umeå University.

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Extensive research on ALS has been pursued at Umeå University since 1992. The objective is to use new knowledge about the mechanisms behind the disease in order to develop therapies for ALS. The main focus is on molecular biological and genetic aspects of the disease and mutations in SOD1 and other genes. Resources (funding, staffing) do not allow any attempted treatment of patients at present.

The research team at Umeå consists of 23 people in four subgroups, directed by Associate Professor Peter Andersen (genetic research), Associate Professor Thomas Brännström (neuropathology), Professor Stefan Marklund (free radicals and cell research), and Associate Professor Henrik Antti (metabolomics).

Anna Birve, post-doctoral fellow, at phone: +46 (0)90-785 29 47 or e-mail:
Associate Professor Peter M. Andersen, phone: +46 (0)90-785 00 00 (exchange,
please page) or e-mail:
References: Michael A van Es, Paul WJ van Vught, Hylke M Blauw, Lude
Franke, Christiaan GJ Saris, Ludo Van Den Bosch, Sonja W de Jong,
Vianney de Jong, Frank Baas, Ruben van 't Slot, Robin Lemmens,
Helenius J Schelhaas, Anna Birve, Kristel Sleegers, Christine Van
Broeckhoven, Jennifer C Schymick, Bryan J Traynor, John HJ Wokke,
Cisca Wijmenga, Wim Robberecht, Peter M Andersen, Jan H Veldink, Roel
A Ophoff, & Leonard H. van den Berg:
Genetic variation in DPP6 is associated with susceptibility to
amyotrophic lateral sclerosis
Facts about ALS
The cause of the disease is unknown, but c. 10-12% of cases involve one of several hereditary variants of the disorder. In Sweden 200-220 people contract the illness each year. People of various ages are afflicted. The most common age is 50-70 years. Twice as many men as women suffer from the disorder.

The average survival time is 2.5-3 years, but some few patients live >10 years with the disease. There is no curative treatment. As of 1996 there is a medicine that slows down the course of the disease and can extend survival by a few months.

The effect is greatest if the medicine is introduced at an early stage of the illness. Nowadays there are special ALS teams that work to provide patients and their loved ones with the best possible help.

Bertil Born | idw
Further information:

Further reports about: DNA DPP6 Umeå

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